EA012091B1 - Medical device comprising a reticulated composite material - Google Patents

Abstract

The present invention relates to medical devices, particularly for therapeutic and/or diagnostic purposes, comprising porous reticulated composite materials and methods for the production thereof. Particularly, the present invention relates to a medical device comprising a porous composite material, said material being obtainable by a process comprising the steps of providing a liquid mixture, comprising at least one inorganic and/or organic reticulating agent; and at least one matrix material selected from polymers or polymer mixtures; and solidifying said mixture.

Description

This invention relates to medical devices, especially for therapeutic and / or diagnostic purposes. In particular, this invention relates to a medical device comprising a porous composite material, said material being obtained by a method comprising the steps of preparing a liquid mixture containing at least one inorganic and / or organic agent forming a network structure and at least one matrix material selected from polymers or mixtures of polymers; and curing the mixture.

Background of the invention

Porous materials play an increasing role in various areas of biomedical technology in the preparation of implantable materials and as carriers of drugs, etc.

The use of composites allows you to combine different materials with different physicochemical properties; a composite material is obtained that has completely new or at least improved properties. Thus, composites can have the same or greater stability, biocompatibility and / or strength with a lower total weight as compared to non-composite materials.

Usually porous composite materials are obtained by sintering. Powders, including fibers, dendritic or spherical precursor particles, are pressed into molds or extruded and then sintered. For such materials, the stiffness, pore size and surface area depend on the packing density, size, shape and composition of the particles in the powders used.

One of the drawbacks of these methods is that the pore size is difficult to control, and the mechanical properties are not sufficiently regulated, especially depending on the pore size and the degree of surface porosity. In particular, the parameters of the sintering process have an effect on the strength, pore size and surface of porous materials. Typically, the pore size has to be adjusted subsequently in additional processing steps, for example, by vapor deposition, electroplating or non-electric cladding to reduce the size of large pores when additional material is added to improve the homogeneous distribution of pore size. These methods, however, lead to a decrease in the available surface area of these materials. Other methods are based on coating by spraying on pre-sintered porous materials of the suspension, followed by drying and re-sintering. These methods lead to the diffusion of material from the suspension into the pores of the porous sintered material and to the insufficient adhesion of the material deposited in the second stage, caused, in particular, by different thermal coefficients of expansion and contraction of the material.

According to the international application \ ¥ O 04/054625, already pre-sintered porous material is coated with a powder of a material with nanoparticles and then subjected to repeated sintering. In the international application \ ¥ O 99/15292, porous composite structures containing fibers are obtained from a dispersion of fibers using binders followed by gasification of the mixture before, during and after sintering.

Another disadvantage of the above methods is that sintering methods are usually carried out at high temperatures, which leads to problems, for example, in obtaining coatings on medical devices that are not sufficiently thermostable. For example, stents derived from memory alloys or artificial heart valves made from polymeric materials are quite sensitive to extreme temperatures. Consequently, the disadvantage of these methods is that the material is processed by expensive molding methods to produce stable two- and three-dimensional structures, and usually only a limited number of forms are possible due to the fragility of the materials.

Further, the processing of materials in accordance with conventional methods often requires several additional stages after processing, and the sintering process is essentially limited to inorganic composites due to the necessary conditions used.

Summary of Invention

There is a constant need to obtain porous coatings on medical devices with improved properties, especially materials that can adapt in their physicochemical properties, such as biocompatibility, to the specific conditions of use in certain areas. In addition, there is a constant need for additional functionalization of porous coatings on medical devices or the device’s construction material itself, for example, in imparting properties to generate signals that allow detection of devices with coatings by various methods.

In addition, there is a need for medical devices containing functional porous materials, and a method for producing them in an economical manner.

Among the several objectives of this invention, one of the objectives is to create a medical device with a functional coating, which is obtained, for example, on the basis of organic and / or inorganic particles in combination with suitable matrix materials, which has easily modifiable properties.

- 1 012091

Another goal is to obtain, for example, an improved medical device, partly consisting of a material, the properties of which can be set according to the intended use of the device.

Another object of the invention is to obtain, for example, adjustable, preferably self-organizing structural properties of the coating, for example, the possibility of obtaining on the basis of the same material any possible two- or three-dimensional coating structure, as well as a finely dispersed structure, for example, it is desirable to control the porosity, preferably without deterioration of chemical and / or physical stability of the material.

Another object of the present invention is to create, for example, a medical device made from a material that can be used both as a coating and as a bulk material having desirable properties.

Another objective of the invention is to create a medical device, fully or partially made of a functional porous composite material having the desired properties.

Another object of the invention is, for example, to provide a method for producing porous mesh composite materials that can be obtained from cheap raw materials with a wide variety of properties in an economical way, preferably involving only a few steps.

Another objective of the present invention is, for example, to create a method for manufacturing medical devices or coatings on such devices obtained from porous composite materials, which allow individual control of biocompatibility, thermal expansion coefficient, electrical, dielectric, conductive or semiconducting and magnetic or optical properties and any combination of them.

For example, these and other objects of the invention can be achieved in accordance with one embodiment of the invention, which provides for a medical device comprising a porous composite material, wherein said composite material includes at least one agent forming a network structure and at least one matrix material and the matrix material contains at least one organic polymer. The reticulating agent may be embedded in the matrix material.

According to another embodiment of the invention, a medical device as described above is provided, wherein said composite material is obtained by a method comprising the steps of:

a) obtaining a liquid mixture, including

ί) at least one agent forming the network structure; and ΐΐ) at least one matrix material containing at least one organic polymer; and

b) curing the specified mixture.

According to another embodiment of the invention, a medical device is provided comprising a coating which comprises a porous composite material, said composite material comprising at least one agent forming a network structure and at least one matrix material, and the matrix material contains at least one organic polymer.

The medical device may partially consist of a composite material, it may be completely made of this composite material and it may, for example, have a coating based on this composite material that can cover at least part of the surface of the device.

According to another embodiment of the invention, the porous composite material may have a porous mesh structure with a pore size in the range from 1 nm to about 400 microns, or alternatively a pore size in the range from about 500 nm to about 1000 microns.

According to another variant of the invention, the device may include an agent that forms a network structure in the form of particles, such as nano - or microcrystalline particles.

In another embodiment of the invention, the agent that forms the grid included in the composition of the device may be in the form selected from tubes, fibers or wire.

According to further embodiments of the invention, the mesh forming agents used in the devices described above may be in the form of particles, such as nanoparticles, as well as microcrystalline particles, which may contain particles in the form of fractions with at least two particle sizes of the same or different materials, and the fractions differ in size from each other by at least 1.1 or at least 2 times. Mesh-forming agents can be in the form of tubes, fibers or wires.

According to further embodiments of the invention, the mesh forming agents included in the devices described above may include inorganic materials, such as metals, metal compounds, metal oxides, semiconducting metal compounds, carbon products such as carbon fiber, graphite, carbon black, carbon black, fullerenes or nanotubes; or materials

- The netting structure may include particles of organic materials or fibers from organic materials such as polymers, oligomers or prepolymers, for example, a synthetic homopolymer or copolymer of an aliphatic or aromatic polyolefin, for example polyethylene or polypropylene, or a biopolymer.

According to other embodiments of the invention, the reticulatory agents incorporated in the devices described above may include at least one inorganic material in combination with at least one organic material or a combination of at least one particulate material with at least one material having the form selected from tubing, fiber or wire.

In accordance with other embodiments of the invention, the matrix materials included in the devices described above may include oligomers, polymers, copolymers or prepolymers, thermosetting resins, thermoplastics, synthetic rubbers, extrudable polymers, formable polymers or compressible polymers, such as, for example, epoxy resins , phenolic resins, alkyd resins, epoxy polymers, poly (meth) acrylate, unsaturated polyesters, saturated polyesters, polyolefins, rubber latexes, polyamides, polycarbonates, polystyrene, polyphenol, polysil icons, polyacetal, cellulose or cellulose derivatives.

According to further embodiments of the invention, the devices described above are selected from implants suitable for insertion into a human or animal body, for example from medical devices or implants for therapeutic or diagnostic purposes, selected from at least one of vascular endoprosthesis, stents, coronary stents, peripheral stents, surgical implants, orthopedic implants, orthopedic bone prostheses, joint prostheses, bone substitutes, vertebral substitutes in the thoracic or explanatory hydrochloric spine; artificial heart, artificial heart valves, subcutaneous implants, intramuscular implants, implantable drug delivery devices, catheters, spring guides for catheters or their parts, surgical instruments, surgical needles, screws, nails, clamps, brackets, substrates for the cultivation of living material or cellular frame for growing fabrics.

In yet another embodiment of the invention, the devices described above may include active agents that can be released from a device in a controlled manner, selected from biologically active agents, which may include microorganisms, viral vectors, cells or living tissue, therapeutically active agents that may preferably dissolve or extracted from a composite material in the presence of physiological fluids, or from agents for diagnostic purposes, such as a marker, contrast media or a radiopaque material that can be detected or which generates a signal detectable by physical, chemical or biological detection methods, such as x-ray, nuclear magnetic resonance (NMR), computed tomography, scintigraphy, single-proton emission computed tomography (BREST), ultrasound, radio frequency research (NOT) or optical coherence tomography (OCT).

Further, according to other embodiments of the invention, the agents forming the network structure included in the devices described above can be selected from materials capable of forming a structure resembling a grid and / or capable of self-orienting to form a three-dimensional structure.

According to another embodiment of the invention, a medical device as described above is provided, which may be a stent, a drug-releasing stent, an implant for drug delivery, an orthopedic implant that releases the drug.

According to other embodiments of the invention, the composite material of a medical device may contain an agent that forms a network structure selected from at least one ingredient from carbon black, fullerenes, carbon fibers, silicon dioxide, titanium dioxide, metal particles, tantalum particles or polyethylene particles, and the matrix material can be selected from at least one of epoxy resins or phenoxy resin.

Such a device and its part, in particular a coating on it, for example, can be obtained from a liquid mixture containing at least one organic solvent, which hardens when the solvent is removed by heat treatment without decomposition of the matrix material.

According to other embodiments of the invention, it is provided to use a medical device, such as described above, as a carrier for culturing cells and / or tissue ίη νίνο or ίη νίίτο, for example, as a cell skeleton for tissue production, while the device can use a living organism or be in bioreactor.

According to other embodiments of the invention, the composite material stage of the device described above can be obtained by a method including a curing step, which may include heat treatment, drying, drying during freezing, applying a vacuum, for example evaporating the solvent or crosslinking, and the crosslinking may be caused by chemical, thermal methods or irradiation.

According to further embodiments of the invention, the composite material of the device described above can be obtained by a method where the curing can include phase separation in a liquid mixture.

- 3 012091 C, containing the agent that forms the mesh, and the matrix material on the solid and liquid phases or the deposition of solid particles from the liquid mixture, for example, before or when removing the solvent and / or stitching the matrix material.

In other embodiments, phase separation or precipitation used in the methods for producing the composite material of the device described above may be caused by an increase in the viscosity of the liquid mixture, which may be caused, for example, by cross-linking, curing, drying, rapid temperature increase, rapid temperature decrease or rapid removal. solvent.

According to preferred embodiments of the invention, the matrix material practically does not decompose during the production of the composite material of a medical device.

According to other embodiments of the invention, the liquid mixture used in the methods for producing the composite material of the devices described above may include at least one crosslinking agent that can be chosen so that the crosslinking during the processing of the liquid mixture prior to the curing stage practically does not change the viscosity the system and / or crosslinking reaction begins almost exclusively during curing.

According to some embodiments of the present invention, it has been found that improved medical devices can be obtained from a composite material having a mesh porous structure obtained by a method that provides a greater opportunity to individually adjust the physicochemical properties of the material and which can be easily adapted for use in certain areas in therapy and diagnosis. In particular, it was found that the degree of porosity, as well as the pore size of a composite material suitable for coating or manufacturing medical devices, can be selectively regulated by the methods described in this application, for example, by proper selection of the number and type of agents forming the network structure, their geometry and particle size, as well as, for example, by combining the particles of the agent that forms the network structure, and the particles of the matrix material with different sizes.

In accordance with this invention, biocompatibility, thermal expansion coefficient, electrical, dielectric, conductive or semiconducting and magnetic or optical properties and / or other physicochemical properties can be easily controlled.

Further, it was found that the pore size and morphology of the particles can be influenced, for example, by appropriately selecting the curing conditions, structuring the material from the point of view of porosity. In addition, it was found that composite materials can be obtained by combining agents that form a grid and a suitable matrix material, from which mechanical, electrical, thermal, and optical properties can be selectively controlled, for example, by changing the content of the solid agent that forms the mesh and solid particles of the matrix. the material in the liquid mixture, the type of solvent or mixture of solvents, the ratio of network-forming agents to the matrix material and / or by selecting materials in accordance with their primary size h asytes and their structure and type.

Not based on any particular theory, it can be shown that, for example, due to a suitable choice of conditions in a liquid mixture and especially conditions during curing, particles can be oriented in the form of a solid mesh, which essentially determines the porosity of the composite material obtained. According to some embodiments of the invention, the materials used and the processing conditions can be chosen in such a way that solid particles in the liquid mixture will form a self-assembled network structure, for example, in the form of a grid, before and / or during curing.

In general, it can be assumed that by appropriate selection of mesh-forming agents, for example, mixtures of these agents of different sizes and / or mixtures of particles of an agent that forms a mesh with tubes or wires, a strong tendency to self-aggregation in a liquid mixture can be obtained, this phenomenon can then accelerated, for example, by appropriate selection of the matrix material, solvent, if any, as well as some additives, which results in composite materials, especially suitable for medical devices, in particular and coatings on such devices.

Description of the drawings

The following detailed description, given as an example, but not limiting this invention only to the specific options described, is easier to understand with the help of the accompanying drawings.

FIG. 1 shows a photograph of a layer of a porous composite material according to Example 1 with an increase of 50,000x.

FIG. 2 reflects the photograph obtained by the 8EM method of the material of Example 2 with an increase of 20,000x.

FIG. Figure 3 shows photographs of a stent with a coating of a porous composite material according to Example 3 with an increase of 150x, 1000x, and 5000x (Fig. 3a, b, and c).

FIG. Figure 4 shows photographs of a stent with a coating of a porous composite material according to Example 4 with an increase of 150x, 1000x and 20,000x (Fig. 4a, b and c).

FIG. 5 shows photographs under a microscope of cell cultures grown on cell

- 4 012091 frameworks according to example 5 after 120 minutes, 3 days and 5 days (Fig. 5a, b and c), respectively.

FIG. 6 shows a photograph of a bone substitute in Example 6 with a magnification of 100 x.

FIG. 7 reflects photographs 8EM (Fig. 7a with an increase of 100x and Fig. 7b with an increase of 20,000x) of the material of Example 7.

FIG. 8 are photographs of material from Example 8 with different magnifications.

Detailed Description of the Invention

In accordance with one aspect of the present invention, a medical device is provided that includes a mesh porous composite material obtained by the method described in this application. The composite material may contain at least one agent that forms a mesh structure, and at least one matrix material described in this application, and the agent that forms the mesh structure can be embedded in the matrix material.

The device may consist almost entirely of this composite material. According to an alternative embodiment of the invention, the device is partially composed of a composite material. According to another embodiment, a medical device is provided, wherein this device may have a coating based on a composite material, this coating may be on at least part of at least one surface of the device, or the coating may be on at least one entire surface or on all surfaces of the device.

According to some embodiments, at least one, possibly both substances, of the agent forming the network structure and the matrix material can be a synthetic material, that is, a material of non-natural origin. The extracellular matrix material of biological origin is excluded from the components according to some embodiments of the invention. According to some embodiments of the invention, the composite material can be rigid, almost non-elastic.

According to other embodiments of the invention, the device may be selected from medical devices for therapeutic and / or diagnostic purposes, including implants for insertion into the human or animal body, such as vascular endoprostheses, intraluminal endoprostheses, stents, coronary stents, peripheral stents, surgical and / or orthopedic temporary application implants including surgical screws, plates, nails and other fixation devices, permanent surgical or orthopedic implants, such as ezy bone or joint prostheses, for example artificial hip or knee joint, insert into the glenoid cavity, bone substitute or a vertebral substitute in the thoracic or dorsal part of the spinal column; screws, plates, nails, implantable orthopedic fixation devices, vertebral prostheses and artificial organs, hearts and parts thereof, including artificial heart valves, cardiac pacemaker shells, electrodes; subcutaneous and / or intramuscular implants, depot with active ingredients, microchips, catheters, spring guides for catheters or their parts, surgical instruments, surgical needles, clamps, brackets, etc. According to some preferred embodiments of the invention, the medical device may include stents, coated stents, drug eluting stents, drug delivery implants, orthopedic implants, drug releasing, and the like. In addition, any of the above medical devices include implants containing agents that form signals, markers, or therapeutically active agents.

A medical device can be made, including not completely, from a composite material according to the invention, consist of or include almost any material, in particular, all the materials from which implants are usually made. Examples include amorphous and / or (partially) crystalline carbon, solid carbon material, porous carbon, graphite, carbon composite materials, carbon fibers, ceramics, such as zeolites, silicates, alumina, silica silicates, silicon carbide, silicon nitride, metal carbides, oxides metals, metal nitrides, metal carbonitrides, metal oxycarbides, metal oxynitrides and transition metal oxycarbonitrides such as titanium, zirconium, hafnium, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, yellow zo, cobalt, nickel; metals and alloys of metals, in particular noble metals, such as gold, silver, ruthenium, rhodium, palladium, osmium, iridium, platinum; tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, cobalt, nickel, copper, steel, in particular, stainless steel, shape memory alloys, such as nitinol, nickel-titanium alloy, glass, stone, fiberglass, minerals, natural or synthetic bone, imitation of bone based on alkaline earth metal carbonates, such as calcium carbonate, magnesium carbonate, strontium carbonate, apatites, such as hydroxyapatite, foamed materials, such as polymeric foams, foamed ceramics, etc., materials, which dissolve in physiology Sgiach conditions, such as magnesium, zinc or alloys containing magnesium and / or zinc, as well as any combination of the above materials and combinations thereof with porous composite material as disclosed herein.

In one embodiment of the present invention, the medical device may be a stent made from a material that dissolves under physiological conditions, such as magnesium, zinc, or an alloy containing magnesium and / or zinc. This device may also include a composite material, for example, in the form of a coating that is radiopaque or which includes a mark, for example, metal or metal particles such as silver or gold. The coating can quickly dissolve or peel off from the device, such as a stent, after implantation under physiological conditions, which allows temporary marking. The composite material can then be loaded with therapeutically active ingredients.

The methods for manufacturing a composite material for medical devices described in this application result in the formation of a reticular porous structure of the composite material, which may have an impact on some of the macroscopic properties of the composite material and the device incorporating such a material. Consequently, many of the properties of the medical device of the invention and the composite material included in this device can be better explained with reference to the methods and materials used to make the medical devices described in this application.

According to the method of manufacturing a medical device according to the invention, it is possible to obtain a mixture capable of flowability, containing at least one agent, forming a network structure, at least one matrix material selected from polymers or mixtures of polymers, which can then be cured. Curing can occur, for example, during drying, crosslinking, hardening, drying, practically without decomposition of the matrix material, which practically retains its structural integrity. The mixture may be liquid, in the form of a dispersion, suspension, emulsion or solution, possibly containing a solvent or mixture of solvents.

In one embodiment of the invention, the mixture may contain practically no solvent and retain the liquid form due to the liquid matrix material, which may be in the molten state, i.e., the molten matrix material.

When using the terms a liquid mixture or a mixture capable of fluidity, it should be borne in mind that these terms are interchangeable and they may include any mixture capable of fluidity, either containing or not containing solvent, regardless of its viscosity, i.e. also melts, suspensions or pastes having a high viscosity, including a practically dry flowable powder or flowable mixtures of particles.

The liquid mixture can be obtained by any conventional method, for example, by dissolving or dispersing solid components in at least one solvent or in at least one matrix material in any suitable order, by mixing solids in a dry state with possible subsequent addition of at least one solvent, by melting the matrix material and dispersing at least one network agent in it, possibly before adding at least one solvent or by obtaining a paste or suspension and then diluting them with at least one solvent or dispersing other components in the solvent.

Mesh Agent

According to the present invention, the term grid-forming agent includes materials that can be oriented to form a network structure or a grid-like structure, under the conditions described in this application, to transform a liquid mixture into a porous cured composite material. In some embodiments of the invention, the mesh-forming agents may include materials that are capable of self-orienting or accelerating self-orienting to form a network or structure that is similar to a network. A grid or grid-like structure in the context of the present invention may be any regular and / or irregular three-dimensional structure containing empty spaces, for example, pores. The porous structure of the mesh material may, for example, enable or promote the ingrowth of biological tissue and / or its proliferation in the material, and it may, for example, be used to store and release active agents, diagnostic markers, etc.

At least one mesh forming agent may be selected from organic and / or inorganic materials of any suitable form or any suitable size or from any mixtures thereof.

For example, network forming agents may include inorganic materials such as zero-valence metals, metal powders, metal compounds, metal alloys, metal oxides, metal carbides, metal nitrides, metal oxynitrides, metal carbonitrides, metal oxycarbides, metal oxynitrides, oxycarbonitrides metals, organic and inorganic metal salts, including alkali and / or alkaline earth metal and / or transition metal salts, including carbonates, sulfates, alkali metal and alkaline earth metal sulfites llov, semiconducting metal compound including the transition metal compounds and / or metals from the main group of the periodic system; metal-based core-shell nanoparticles, glass and glass fibers, carbon and carbon fibers, silicon, silica, zeolites, titanium oxides, zirconium oxide, aluminum oxide, aluminum silicates, talc, graphite, carbon black, lamp soot, furnace soot, gas carbon black, carbon black, minerals, phyllosilicates, or any mixtures thereof.

Biodegradable metal-forming agents, based on metals, selected from alkali or alkaline earth metal salts, can also be used, they can be compounds based on

- 6 012091 magnesium or zinc or the like or nanoalloys or any mixture thereof. The agents forming the network structure of some embodiments of the present invention may be selected from salts, oxides or alloys of magnesium, which can be used in biodegradable coatings or molded products, including implant products or coatings on an implant that is capable of decomposition under the influence of liquids which can then lead to the formation of magnesium ions and hydroxyapatite.

Some net-forming agents may include, but without limitation, powders, preferably nanomorphic nanoparticles, metals with zero valence, metal oxides, and combinations thereof, for example metals and metal compounds selected from the main group of metals of the Periodic Table, transition metals, such as copper, gold and silver, titanium, zirconium, hafnium, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium or platinum, or from rare earth x metals. Metal-based compounds may include, for example, organometallic compounds, metal alkoxides, carbon particles such as carbon black, lamp black, flare carbon black, carbon black, carbon black, graphite, carbon fibers or diamond particles, and the like. Other examples include metal-containing endohedral fullerenes and / or endometallofullerenes, including these compounds based on rare-earth metals such as cerium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, iron, cobalt, nickel, manganese, and mixtures thereof, such as mixtures of iron with platinum or alloys. Magnetic, supermagnetic or ferromagnetic metal oxides, such as iron oxides and ferrites, such as cobalt, nickel or manganese based ferrites, can also be used. Magnetite metals or alloys, such as ferrites, for example, gamma-iron oxide, magnetite, or Co, N1 or Mn, can be used to produce materials with magnetic, supermagnetic, ferromagnetic, and signal-forming properties. Examples of such materials are described in international applications AO 83/01738, AO 88/00060, AO 85/02772, AO 89/03675, AO 90/01295 and AO 90/01899 and in US Patent Nos. 4452773, 4675173 and 4770183. At least At least one net-forming agent may include any combination of materials listed above and below.

In addition, semiconducting compounds or nanoparticles, including semiconductors of the ΙΙ-νΐ groups, ΙΙΙ-ν groups, or group IV of the Periodic System, can be used as an agent that forms the network structure, in some embodiments of the present invention. Acceptable PMP semiconductors! The groups include, for example, Mdg, Mdge, MdTe, Ca8, Ca8e, CaTe, 8t8, 8tTe, 8t8e, Ba8, Ba8e, BaTe, Ζηδ, Ζηδe, ηTe, C68. Sb8e, SbTe, Nd8, Nd8e, NdTe or a mixture thereof. Examples of semiconductors of the У-групп groups include, for example, CaAk, CaNo CaR, Ca8b, HCaAc, ΙηΡ, ΙηΝ, Ιηδϋ, ΙηΆδ, A1Ak, Α1Ρ, A18b, Α1δ, and mixtures thereof. Examples of semiconductors of the PG group include germanium, lead, and silicon. You can also use combinations of any of the semiconductors listed above.

In some embodiments, it may be preferable to use complex metal-based nanoparticles as agents forming a network structure. These may include, for example, so-called core-shell configurations, which are described by Repd e! a1. In Yeryah1a1 Sgo \\ I1 og ShdYu bitsheksekep! Sat / Sat / Satd Sote ^ Je11 No. logging1/5/1

Semiconductive nanoparticles can be selected from the materials listed above, they can contain a core with a diameter of about 1-30 nm or preferably about 1-15 nm, then semiconducting nanoparticles can crystallize to a depth of about 1-50 monolayers or preferably about 1-15 monolayers. Kernels and shells can be of the combinations listed above, including kernels from Sat δe or SbTe and shells from Satδ or πδ.

According to another embodiment of the present invention, the mesh forming agents may be selected based on their absorption properties for radiation at wavelengths from gamma radiation to microwaves or based on their ability to emit, especially at wavelengths from about 60 nm or less. . By proper selection of the agents that form the network structure, non-linear optical properties can be obtained. These can be materials that can block IR radiation at specific wavelengths, which is suitable for labeling purposes or for obtaining therapeutic implants that absorb radiation. The agents forming the grid, the size of their particles and the diameters of their cores and shells can be chosen so as to obtain compounds emitting photons, while this emission takes place at a wavelength in the range from about 20 to 1000 nm. Alternatively, you can choose a mixture of suitable compounds that emit photons at different wavelengths during irradiation. In one embodiment of the present invention, fluorescent compounds based on metals that do not require quenching can be selected.

In one embodiment of the invention, at least one agent that forms a network structure may be selected from carbon particles, such as nanomorphic carbon particles, such as fullerenes, such as C36, C60, C70, C76, C80, C86, C112, etc. . or any mixtures thereof; such as multi-, single or single-block nanotubes, for example, MAH, ΌΧΟΝΈ δАNТ, randomly oriented nanotubes, as well as so-called fullerene onion structures or metallofullerenes or simply of graphite, soot, carbon black, etc.

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In addition, the network forming agents may include organic materials such as polymers, oligomers or prepolymers; shellac, cotton or fabrics and any combination thereof.

According to other embodiments of the invention, the agent that forms the grid may contain a mixture of at least one inorganic and at least one organic material.

In addition, the agents that form the grid, on the basis of the materials mentioned, can be chosen from among particles, i.e. substances having a substantially spherical or sphere-like irregular shape, or from fibers. They can be in the form of nano- or microcrystalline particles, powders and nanowires. These agents can have particles with an average size of from about 1 nm to about 1000 microns, preferably from about 1 nm to 300 microns, or more preferably from about 1 nm to 6 microns. These particle sizes are characteristic of all materials that can be used as the mesh forming agents described in this application.

The agents forming the network structure may include at least two kinds of particles of the same or different materials, which differ in size from each other by at least 2, or at least 3, or 5 times, sometimes at least least 10 times. Not based on any particular theory, it is believed that the difference in particle sizes may contribute to the self-orientation of the agents that form the grid, when a network is formed.

In some embodiments, the mesh forming agents include a combination of carbon particles, such as soot, carbon black, or lamp soot, with fullerenes or fullerene mixtures. Carbon particles can have an average size of from about 50 to 200 nm, for example from about 90 to 120 nm. In yet another embodiment, the at least one mesh-forming agent includes a combination of metal oxide particles, such as silica, alumina, titanium oxide, zirconium oxide, or zeolites, or combinations thereof, with fullerenes or fullerene mixtures. The metal oxide particles may have an average size of from about 5 to 150 nm, for example, from about 10 to 100 nm. In some embodiments of the invention, the at least one mesh-forming agent may include a combination of at least one metal powder with metal oxide particles, such as silica, alumina, titanium oxide, zirconia, zeolites, or a combination thereof. The metal oxide particles may have an average size of from about 5 to 150 nm, for example, from about 10 to 100 nm, and the metal powder may have particles with an average size in the micrometer range, for example, from about 0.5 to 10 microns or from about 1 to 5 microns. All of these agents, forming a grid, can be connected, for example, with epoxy resins as the matrix material, preferably thermally curable and / or stitched phenolic resins.

In addition, at least one mesh forming agent can also be in the form of tubes, fibers, fibrous materials or wires, in particular nanowires made of any material mentioned above. Examples include carbon fibers, annotates, glass fibers, metallic nanowires or metallic micro-products. Such forms of mesh forming agents can have an average length of from about 5 nm to 1000 μm, for example, from about 5 nm to 300 μm, for example from about 5 nm to 10 μm, from about 2 to 20 μm, and / or the average diameter from about 1 nm to 1 μm, for example, from about 1 to 500 nm, from 5 to 300 nm, or from about 10 to 200 nm.

Particle size can be specified as average and can be determined by laser methods, such as the TOT method (transition time), for example, on the C18 Parameter Type Analyzer on the ApkegashM analyzer. Other methods for determining particle size include powder diffraction or TEM (transmission electron microscopy).

In some embodiments, solvent-free mixtures can be used, wherein the matrix material can be, for example, liquid prepolymer or a melt, i.e. a molten matrix material, which is then cured, for example, by crosslinking or curing.

In some embodiments, the mesh forming agent and the matrix material do not contain fibers or fibrous materials, and the resulting composite material is substantially free of fibers.

In other embodiments, it may be preferable to modify the agents that form the mesh, for example, to improve their dispersibility or wettability in solvents or in the matrix material, in order to obtain additional functional properties or improve compatibility. Methods for modifying particles or fibers, if necessary, are well known to those skilled in the art and can be applied depending on the requirements for the individual composition and the materials used. For example, silanes, such as organosilanes, can be used to modify mesh-forming agents. Suitable organosilanes and other modifying agents are described, for example, in international application PCT / EP 2006/050621 and in patent application US No. 11/346983, these agents can also be used in this invention, as well as substances that are cross-linking agents.

In some embodiments of the present invention, the mesh forming agents can be modified, for example, with at least one component of alkoxides, metal alkoxides, colloidal particles, in particular metal oxides, etc. Metal alkoxides have the general formula M (OK) _X , where M denotes any metal alkoxide, which can, for example, be hydrolyzed and / or polymerized in the presence of water. K denotes alkyl containing from 1 to about 30 carbon atoms, which may be linear, branched, and x denotes a value equivalent to va

- 8 012091 laze metal ion. You can also use metal alkoxides, such as 81 (S) ₄ , T1 (S) ₄ , A1 (S) ₃ , τ (ΟΒ) ₃ and 8n (S) ₄ . Specifically, B may be methyl, ethyl, propyl or butyl. Other examples of suitable metal alkoxides may include T1 (isopropoxy) ₄ , A1 (isopropoxy) ₃ , A1 (sec. Tops) ₃ , Ζ ^ (n-butoxy) _4, and Ζ ^ (Η-propoxy) ₄ .

Other suitable modifying agents may be selected from at least one of silicon alkoxides, such as tetraalkoxysilanes, where the alkoxy may be branched or linear and may contain from 1 to 25 carbon atoms, for example, from tetramethoxysilane (TMO8), tetraethoxysilane (TEO8) or tetra-n-propoxysilane, as well as their oligomeric forms. Alkyloxane is also available. , isobutyltriethoxysilane, isobutyltrimethoxysilane, octyltriethoxysilane, octyltrimethoxysilane, which produces Edise AC, Setshapu, methacryloxide Acyltrimethoxysilane (ME1M8); aryltrialkoxysilanes, such as phenyltrimethoxysilane (RTMO8), phenyltriethoxysilane, produced by Edisza AC, Segtapu; phenytropoxy N- (n-butyl) -3-aminopropyltrimethoxysilane, 3-aminopropylmethyldiethoxysilane, 3-glycidyloxypropyltrimethoxysilane, 3-glycidyloxypropyltriethoxysilane, vinyatrimethoxysilane, vinyltriethoxysilane, for the sake of the first part, of lans; (meth) acrylsilanes, phenylsilanes, silane oligomers and polymers, epoxysilanes; fluoroalkylsilanes, such as fluoroalkyltrimethoxysilanes, fluoroalkyltriethoxysilanes, with partially or fully fluorinated linear or branched fluoroalkyl residues containing from about 1 to 20 carbon atoms, for example, tridecafluoro-1,1,2,2-tetrahydrooctyltriethoxysilane, akidnnnnnnnnnurs apr. Eupazu1ap® P8800 and P8815; and mixtures thereof. In addition, 6-amino-1-hexanol, 2- (2-aminoethoxy) ethanol, cyclohexylamine, butyric acid cholesteryl ester (PCBCB), 1- (3-methoxycarbonyl) propyl-1-phenyl ether or combinations can also be used.

It should be noted that usually the above modification agents and silanes can also be used as crosslinking agents, for example, at the curing stage for curing (curing) the liquid mixture.

In yet another embodiment, the at least one mesh forming agent includes particles or fibers of polymers, oligomers or prepolymers of organic substances. These particles or fibers can be obtained by conventional polymerization methods to obtain discrete particles, for example by polymerization in a liquid medium in emulsions, dispersions, suspensions, or in solutions. In addition, these particles or fibers can also be obtained by extrusion, spinning, granulating, grinding or grinding polymeric materials. If the reticulating agent is selected from particles or fibers of polymers, oligomers, prepolymers, thermoplastics or elastomers, these materials can be selected from homopolymers or copolymers described below for use as matrix materials. These polymers can be used as a matrix material if they are not particles or fibers, or as a network forming agent if they are in the form of particles or fibers. The polymeric agents forming the network structure can be chosen among those that can decompose at elevated temperatures and thus can act as pore-forming agents in the network materials. Examples include polyolefins, such as polyethylene or polypropylene in the form of particles or fibers.

According to some variant of the agent, forming a mesh structure may be electrically conductive polymer, described below as the electrically conductive matrix material.

According to other embodiments of the present invention, at least one agent forming the network structure may include, for example, non-polymeric particles encapsulated in a polymer, wherein the non-polymeric particles may be selected from the materials described above. Polymerization methods for encapsulating non-polymeric particles of a reticulating agent include any suitable conventional polymerization methods, for example, radical or non-radical polymerization, enzymatic or non-enzymatic polymerization, for example polycondensation. Encapsulating the particles of the reticulating agent, depending on the individual components used, can result in covalently or non-covalently encapsulated particles of the reforming agent.

For combining with the matrix material, the encapsulated agents can be in the form of polymer spheres, in particular nano-size or micro-size spheres, or dispersed, suspended or emulsified particles or capsules, respectively. To obtain particles encapsulated in a polymer according to this invention, any conventional method can be used. Suitable

- 9 012091 methods of encapsulation and the materials and conditions used for this are described, for example, in international applications PCT / EP 2006/060783 and PCT / EP 2006/050373 and US patent applications No. 11385145 and 11339161. These methods, materials and methods can applied according to variants of the present invention.

Suitable encapsulation methods are described, for example, in Australian application No. Au 9169501, EP applications 1205492, EP 1401878, EP 1352915 and EP 1240215, in US patent No. 6380281, in US patent application No. 2004192838, in Canadian patent CA 1336218, patent SI 1262692T , CB patent No. 949722 and application 10037656 and in other documents cited in this context, for example, in international applications PCT / EP 2006/060783 and PCT / EP 2006/050373, as mentioned above.

Encapsulated agents forming a network structure can be obtained in the form of particles ranging in size from about 1 to 500 nm or in the form of microparticles with an average size of from about 5 nm to 5 microns. Agents that form a network structure can also be encapsulated in mini or microemulsions of suitable polymers. The terms mini- and microemulsion refer to dispersions containing an aqueous phase, an oily or hydrophobic phase, and one or more surfactants. Such emulsions may include suitable oils, water, one or more surfactants, possibly one or more concomitant surfactants, and / or one or more hydrophobic substances. Mini-emulsions can include aqueous emulsions of monomers, oligomers or prepolymers, stabilized by surfactants that can easily polymerize, and the size of the emulsified droplets can be from about 10 to 500 nm or more.

Mini-emulsions of encapsulated network-forming agents can also be made in a non-aqueous medium, for example, in formamide, glycol and non-polar solvents. The prepolymers may include thermosetting resins, thermoplastics, plastics, synthetic rubbers, extrudable polymers, formable polymers, etc., or mixtures thereof, including prepolymer reagents, from which poly (meth) acrylates can be used.

Examples of suitable polymers for encapsulating agents that form a network structure may include, but are not limited to, homopolymers or copolymers of aliphatic or aromatic olefins such as polyethylene, polypropylene, polybutene, polyisobutene, polypentene, polybutadiene, polyvinyl polymers such as polyvinyl chloride or polyvinyl alcohol, poly (meth) acrylic acid, polymethyl methacrylate (PMMA), polyacrylcyanacrylate, polyacrylonitrile, polyamide, polyester, polyurethane, polystyrene, polytetrafluoroethylene; biopolymers such as collagen, albumin, gelatin, hyaluronic acid, starch, cellulose, such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylphthalate cellulose; casein, dextran, polysaccharide , polyanhydrides, polyphosphazenes, polyamino acids, ethylene copolymer with vinyl acetate, silicones, polyether-based polyetherurethanes, polyether-based polyetherurethanes, polyethers, polyethers, such as polyethers tilenoksid, polypropylene oxide, pluronics, polytetramethylene glycol; polyvinylpyrrolidone, poly (vinyl acetate phthalate), shellac, and combinations of these homopolymers or copolymers; with the exception of cyclodextrin and its derivatives or similar carriers.

Other encapsulating materials include poly (meth) acrylate, unsaturated polyester, saturated polyester, polyolefins such as polyethylene, polypropylene, polybutene, alkyd resins, epoxy polymers, epoxy resins, polyamide, polyimide, polyetherimide, polyamidoimide, polyether imide, polyamide, polyimide, polyetherimide, polyamide imide, polyether imide, polyester, polyimide, polyimide, polyetherimide, polyamide imide, polyether imide, polyester, polyamide, polyimide, polyether imide, polyamide imide, polyester imide, polyester, polyamide, polyimide, polyether imide, polyamide imide, polyester imide, polyamide polyamide polycarbonate, polystyrene, polyphenol, polyvinyl ether, polysilicone, polyacetal, cellulose acetate, polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polysulfone, polyphenylsulfone, polyethersulfone, polyketone, oliefirketon, polybenzimidazole, polybenzoxazole, polibenztiazol, polyfluorohydrocarbons, polifenilovy ether, polyarylate, cyanate ester polymer, or mixtures or copolymers of any of the above compounds.

In some embodiments of the invention, the polymers used to encapsulate the reticulating agents may include mono (meth) acrylate, di (meth) acrylate, tri (meth) acrylate, tetraacryl, and pentaacrylate-containing poly (meth) acrylates. Examples of a mono-chemical composition of the product are those of the , 2-dimethyl-3-hydroxypropyl acrylate, 5-hydroxypentyl methacrylate, diethylene glycol monomethacrylate, trimethylolpropane monomethyl acrylate, pentaerythritol monomethacrylate, hydroxymethyl ovated N- (1,1-dimethyl-3-oxobutyl) acrylamide, Ν-methylolacrylamide,-methylol methacrylamide, N-ethyl-N-methylol methacrylamide, I-ethyl-Imethylol acrylamide, Ν,-dimethylol acrylamide, -Ν-e-metholyl acrylamide, Ν,-dimethylol acrylamide, -Ν-e-metholyl acrylamide,,-dimethylol acrylamide, -Ν-e-methylol acrylamide, Ν,-dimethylol acrylamide,--e-metholyl acrylamide, Ν,-dimethylol acrylamide, -e-ethylacrylamide,,-dimethylol acrylamide, -e-ethylacrylamide,,-dimethylol acrylamide, -e-ethylacrylamide; propanolakrilamid, Νmetilolakrilamid, glycidyl acrylate and glycidyl methacrylate, methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, amilakrilat, ethylhexyl acrylate, octyl acrylate, t, octyl acrylate, 2-methoxy-10 012 091 ethyl acrylate, 2-butoksietilakrilat, 2-phenoxyethyl acrylate, chloroethyl acrylate, tsianetilakrilat, dimethylaminoethyl acrylate, benzyl acrylate, methoxy benzyl acrylate, furfuryl acrylate, tetrahydrofurfuryl acrylate and phenyl acrylate; di (meth) acrylates can be selected from 2,2-bis- (4-methacryloxyphenyl) propane, 1,2-butanediol diacrylate, 1,4-butanediol diacrylate, 1,4-butanediol dimethacrylate, 1,4-cyclohexanediol dimethacrylate, 1,10- decadioclion - (2-hydroxy-3 etakriloksipropoksi) phenyl] propane, bis (2-metakriloksietil) -H, F-1,9-nonilenbiskarbamata, 1,4tsiklogeksandimetanoldimetakrilata diakriluretanovyh and oligomers; three (meth) acrylates can be selected from tris- (2-hydroxyethyl) isocyanurate trimethacrylate, tris- (2-hydroxyethyl) isocyanurate triacrylate, trimethylolpropane trimethacrylate, trimethylolpropane triacrylate or pentaerythritol triacrylate; tetra (meth) acrylates can be selected from pentaerythritol tetraacrylate, ditrimethylol propane tetraacrylate or ethoxylated pentaerythritol tetraacrylate; suitable penta (meth) acrylates can be selected from dipentaerythritol pentaacrylate or pentaacrylate esters, as well as mixtures, copolymers, or combinations of any of these compounds. Biopolymers or acrylates can also be used to encapsulate agents that form a network structure, according to some embodiments of the invention, for example, in biological or medical fields.

Encapsulating reagents may include polymerizable monomers, oligomers or elastomers, such as polybutadiene, polyisobutylene, polyisoprene, poly (styrene-butadiene-styrene), polyurethanes, polychloroprene, natural rubber, gums, such as gum arabic, a tree, a tree, a tree, a tree, a tree. or silicones and mixtures thereof, copolymers or any combinations. The network forming agents can be encapsulated in elastomers, alone or in mixture with thermoplastic and elastomer, or in an alternating sequence of thermoplastic and elastomeric shells or layers.

The polymerization reaction for encapsulating the reticulating agents can be any suitable polymerization reaction, for example, radical or non-radical polymerization, enzymatic or non-enzymatic polymerization, including polycondensation. The emulsions, dispersions or suspensions used may be in the form of aqueous, non-aqueous, polar or homopolar systems. The amount and size of emulsified or dispersed droplets can be adjusted as required by the addition of suitable surfactants.

Surfactants can be anionic, cationic, zwitterionic or non-ionic, or a combination thereof. Preferred anionic substances can include, but are not limited to, monoglyceride (ether) sulfates, fatty acid amido esters, mono- and dialkyl sulfosuccinates, mono- and dialkyl sulfosuccinates, sul jfc, amidic soaps, carboxylic acid products of plant origin based on wheat and alkyl (ether) phosphates.

Cationic surfactants suitable for encapsulation according to some embodiments of the invention may include quaternary ammonium compounds such as dimetildistearilammoniyhlorid, Yb 81erai1eh® 90 (81erai), quaternary esters, in particular salts trialkanolaminoefirov quaternized fatty acids, salts of long-chain primary amines, quaternary ammonium compounds , such as hexadecyltrimethylammonium chloride (STMA-C1), EekutsiaP® A (cetrimonium chloride, Sodische) or EekutsiaP® BIV 50 (lauryl dimethylbenzylammonium chloride, Sodsh ).

Other preferred surfactants may include lecithin, poloxamers, i.e., block copolymers of ethylene oxide and propylene oxide, including poloxamers of BA8P Co, available under the name Pligox®, including Pligox® Ρ68ΝΡ, and alcohol ethoxylates T \ ueep® series. available in the company 81dsha A1bpsk or Kgasketer 8aepTsPs 1ps. etc.

The reticulating agent may be added before or at the beginning of the polymerization reaction, it may be in the form of a dispersion, emulsion, suspension or solid solution or as a solution of the agent in a suitable solvent or mixture of solvents or as mixtures of these forms. The encapsulation process may involve a polymerization reaction, possibly with the use of initiators, starters or catalysts, in which case an ίη Chi encapsulation of the agents forming the network structure can occur in polymeric capsules, spheres or drops. The content of the solid agent that causes the formation of a net structure in such mixtures for encapsulation, you can choose such

- 11 012091 so that the solids content of the polymer capsules, spheres or drops is from about 10 to about 80% by weight of the active agent.

You can also add agents that form a network structure, after the completion of the polymerization reaction, either in solid or in liquid form. Agents that form a network structure can be selected from those compounds that are capable of binding to spheres or droplets of the polymer, covalent or non-covalent. The droplet size of the polymer and the solids content of the agent can be chosen so that the solids content of this agent ranges from about 5 to about 90 wt.%, Based on the total weight of the polymerization mixture.

In one embodiment of the invention, the encapsulation of the agents that form the network structure can be repeated at least once by adding additional monomers, oligomers or prepolymers after the first polymerization / encapsulation step is completed. By carrying out at least one repeated polymerization step, it is thus possible to obtain multi-coated polymer capsules. In addition, agents forming a network structure associated with polymer spheres or droplets can be encapsulated by the subsequent addition of monomers, oligomers or prepolymers to re-coat these agents with a polymer capsule. Repetition of these stages can provide multi-layered polymer capsules, including an agent that forms a network structure.

Any of the encapsulation steps described above can be combined with other stages. According to a preferred embodiment of the invention, polymer-encapsulated agents forming a network structure can then be subjected to coating based on release modifying agents.

According to other embodiments of the invention, the mesh forming agents or these agents encapsulated into polymers can then be encapsulated into bubbles, liposomes or micelles, or into coatings. Suitable surfactants for this purpose may include those commonly used in the encapsulation reactions described above. Other surfactants include compounds containing hydrophobic groups, which may be hydrocarbon residues or silicone residues, for example, polysiloxane chains, hydrocarbon monomers, oligomers and polymers, or lipids, or phospholipids, or any combination thereof, such as glycerol ethers, such as phosphatidylethanolamine, phosphatidylcholine, polyglycolide, polylactide, polymethacrylate, polyvinyl butyl ether, polystyrene, polycyclopentadienylmethyl norbornene, polypropylene, polyethylene, polyisobutylene, polysiloxane, or another type of surfactant.

In addition, depending on the polymer shell, surface-active agents for encapsulating agents encapsulated in the polymer in bubbles, coatings, etc. may be selected from hydrophilic surfactants or substances having hydrophilic residues or hydrophilic polymers such as polystyrene sulfonic, poly-N-alkilvinilpiridiniygalogenid, poly (meth) acrylic acid, polyaminoacids, poly-N-vinylpyrrolidone, polyhydroxyethylmethacrylate, polyvinyl ether, polyethylene glycol, polypropylene oxide, polysaccharides, for example, agarose, dextran, starch, cellulose, amylase, amylopectin or polyethylene glycol, or polyethyleneimine with a suitable molecular weight. Mixtures of hydrophobic or hydrophilic materials or lipid polymeric compounds can be used to encapsulate the polymer-encapsulated agents that form the network structure into bubbles or to further coat these polymer-encapsulated agents.

In addition, encapsulated agents can be chemically modified by functionalization with suitable linker groups or coatings. For example, they can be functionalized with organosilane compounds or organofunctional silanes. Such compounds for the modification of polymeric encapsulated agents that form a network structure are described above.

The introduction of particles encapsulated in polymers into the materials described in this application can be considered, without considering any particular theory, as obtaining a specific form of an agent forming a network structure. The particle size and size distribution of particles encapsulated in a polymer agent in dispersion or suspended form usually corresponds to the size of the particles and their distribution by size of the finished material encapsulated in the polymer. Polymer-encapsulated particles can be characterized in the liquid phase, for example, by dynamic light scattering methods, with respect to the particle size and monodispersity.

Further, the particles of the network-forming agents of this invention can be encapsulated into biocompatible, preferably biodegradable polymers. For example, biocompatible polymers can be used, indicated in this application as possible materials for the matrix. These materials can also be used directly as agents forming a network structure, as described above.

In some embodiments, pH-sensitive polymers can be used to encapsulate particles of a network-forming agent, or as such an agent itself. For example, pH-sensitive polymers mentioned as possible matrix materials can be used. Further, polysaccharides such as cellulose acetate phthalate, hydroxypropylme

- 12 012091 tilcellulose phthalate, hydroxypropyl methylcellulose succinate, cellulose acetate trimellitate and chitosan.

In some variants, polymers that are temperature sensitive or form thermogels can be used to encapsulate particles of the agent that forms the network structure, or as such an agent itself. Examples of them are listed below when describing the materials of the matrix.

At least one reticulating agent may be combined with the matrix material in a suitable solvent before being converted into a porous composite material according to the invention.

Matrix material.

According to some embodiments of the invention, at least one reticulating agent is combined with matrix materials, possibly in the presence of a suitable solvent or solvent mixture or in the absence of solvents, and the matrix materials can be combined with selected agents or their mixtures to form a porous composite material.

The matrix material may include polymers, oligomers, monomers or prepolymers, possibly of synthetic origin, and the polymers may be the same as the polymers mentioned above as suitable for the agents forming the network structure, or in the quoted sources as suitable for encapsulating the agents forming the network structure , as well as all substances that can be synthesized to obtain prepolymer, partially polymerized or polymeric materials or that already exist as such materials, in particular These are also polymer composites. Polymer composites may already be in the form of nanocomposites or may contain nanomorphic particles in a homogeneous dispersed form, as well as in the form of substances that can be cured from suspensions, dispersions or emulsions and which are suitable for obtaining a composite material with selected agents that form a network structure. The polymers used may include thermosetting resins, thermoplastics, synthetic rubbers, extrudable polymers, formable polymers, etc., and mixtures thereof.

Further, additives can be introduced that improve the compatibility of the components used in the preparation of the composite material, for example, combination agents such as silanes, surfactants or fillers, namely organic or inorganic fillers.

In one embodiment, a polymer suitable for use as a matrix material may include homopolymers, copolymers of prepolymer forms and / or oligomers of aliphatic or aromatic olefins, such as polyethylene, polypropylene, polybutene, polyisobutene, polypentene; polybutadiene, polymers of vinyl compounds, such as polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polyacrylates, including poly (meth) acrylic acid, polymethyl methacrylate (PMMA), polycyanoacrylates; polyacrylonitrile, polyamide, polyester, polyurethane, polystyrene, polytetrafluoroethylene; especially preferred are biocompatible polymers listed below; ethylene-vinyl acetate copolymer, silicones; polyether ethers based on polyethers of polyethers and polymers, polyether ureas, polyethers, such as polyethylene oxide, polypropylene oxide, pluronics, polytetramethylene glycol; polyvinylpyrrolidone, poly (vinyl acetate phthalate), shellac, or combinations thereof.

In other embodiments, the polymer used as the matrix material may include unsaturated or saturated polyesters, alkyd resins, epoxy polymers, epoxy resins, phenolic resins, nylon, polyimide, polyetherimide, polyamide imide, polyether imide imid, polyether imidimide, polyurethane, polycarbonate, polystyrene, polyphenol, polyvinyl ethers, polysilicone, polyacetal, cellulose acetate, polysulfone, polyphenylsulfone, polyethersulfone, polyketone, polyetherketone, polyetheretherketone, polyetherketone polybenzimidazole, polybenzoxazole, polybenzthiazole, polyfluorohydrocarbons, polyphenyl ether, polyarylate, polymers of cyanate esters, copolymers or mixtures of these compounds.

Other polymers suitable as matrix material are polyacrylates, for example poly (meth) acrylates based on mono (meth) acrylate, di (meth) acrylate, three (meth) acrylates of tetraacrylate and pentaacrylate. Examples of mono (2) acrylate dimethyl-3-hydroxypropyl acrylate, 5-hydroxypentyl methacrylate, diethylene glycol monomethacrylate, trimethylolpropane monomethyl acrylate, pentaerythritol monomethacrylate, hydroxymethyl And- (1,1-dimethyl-3-oxobutyl) acrylamide, Ν-methylolacrylamide, ак-methylol methacrylamide, Ν ethyl-N-methylol methacrylamide, Ν-ethyl-M-methylol acrylamide, Ν--dimethylol acrylamide, эт-ethane-methanol amide, Ν--dimethylol acrylamide, Ν-ethane-methanol amide, propanolakrilamid, Ν-methylolacrylamide, glycidyl acrylate and glycidyl methacrylate, methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, amilakrilat, ethylhexyl acrylate, octyl acrylate, tretoktilakrilat, 2-methoxyethyl, 2-butoksietilakrilat, 2-phenoxyethyl acrylate, chloroethyl acrylate, tsianetilakrilat, dimethylaminoethyl acrylate, benzyl acrylate, methoxybenzyl krilat, furfurilakrilat,

- 13 012091 tetrahydrofurfuryl acrylate and phenyl acrylate; di (meth) acrylates can be selected from 2,2-bis- (4 methacryloxyphenyl) propane, 1,2-butanediol diacrylate, 1,4-butanediol diacrylate, 1,4-butanediol dimethacrylate, 1,4-cyclohexanediol dimethacrylate, 1,10-decanediol dimethacrylate, diethylene glycol, dipropylene glycol; (2-hydroxy-3 -methacryloxypropoxy) phenyl] propane, bis- (2-methacryloxyethyl) №№1.9-nonylene biscarbamate. 1,4-cyclohexanedimethanol dimethacrylate and diacrylurethane oligomers; three (meth) acrylates can be selected from tris- (2-hydroxyethyl) isocyanurate trimethacrylate, tris (2-hydroxyethyl) isocyanurate triacrylate, trimethylolpropane trimethacrylate, trimethylolpropane triacrylate or pentaerythritol triacrylate; tetra (meth) acrylates can be selected from pentaerythritol tetraacrylate, di-trimethylol propane tetraacrylate or ethoxylated pentaerythritol tetraacrylate; suitable penta (meth) acrylates can be selected from dipentaerythritol pentaacrylate or pentaacrylate esters, as well as mixtures, copolymers, or combinations of any of these compounds; examples of polyacrylate overclocking; -chlorophenyl acrylate, polycyclohexylacrylate, polydicyclopentenyloxyethylacrylate, poly-2- (K, No. diethylamino) ethyl methacrylate, polydimethylamine neopentyl acrylate, polycaprolactone-2- (methacryloxy) ethyl ether, polyfurfuryl-methyl, polyfurfuryl-polyethylaminoethyl acrylate Poly (ethylene glycol) methacrylate, poiakrilovaya acid and poly (propylene glycol) methacrylate, and mixtures, copolymers and combinations thereof.

Suitable polyacrylates also include polymerized aliphatic unsaturated organic compounds, for example polyacrylamide and unsaturated polyesters obtained by condensation of unsaturated dicarboxylic acids and diols, as well as derivatives of vinyl polymers or compounds containing terminal double bonds. Examples of monomers include vinylpyrrolidone, styrene, vinylnaphthalene or vinylphthalimide. Derivatives of methacrylamide include Ν-alkyl- or Ν-alkylene-substituted or unsubstituted (meth) acrylamide, for example, acrylamide, methacrylamide, Ν-methacrylamide, Ν-methyl methacrylamide, Ν-ethyl acrylamide, Ν, Ν-dimethylacrylamide,-methylacrylamide, Ν-ethyl acrylamide,, Ν-dimethylacrylamide, эти-methylacrylamide,-ethyl acrylamide,,-dimethylacrylamide, Ν-methylacramide, , Ν-etilmetakrilamid, ^ methyl-i-ethylacrylamide, Νizopropilakrilamid, Ν-n-propylacrylamide, Ν-isopropylmethacrylamide, Ν-n-propilmetakrilamid, Νakriloilpirrolidon, Ν-metakriloilpirrolidon, Ν-acryloylpiperidin, Ν-metakriloilpiperidin, Νakriloilgeksagidroazepin, Ν-acryloylmorpholine or Мет-metac Ryloylmorpholine.

Other polymers suitable for the matrix material include unsaturated and saturated polyesters, especially alkyd resins. Polyesters may contain different amounts of saturated or aromatic dibasic acids and anhydrides in the polymer chains, or epoxy resins that can be used as monomers, oligomers or polymers, especially those containing one or more oxirane rings, one aliphatic, are also suitable. aromatic or mixed aliphatic-aromatic molecular structural element or exclusively non-benzoid structures, namely aliphatic or cycloaliphatic structures with by sites, such as halo, ester groups, ether groups, sulfo groups, siloxane groups, nitro groups or phosphate groups, or any combination thereof, with or without these substituents.

According to preferred embodiments of the invention, the matrix material may be an epoxy resin, for example, of the glycidyl type, such as a resin containing diglycidyl groups of bisphenol A. Other epoxy resins include amino group-containing epoxy resins, in particular tetraglycidyl diaminophenylmethane, triglycidyl-p-aminophenol, triglycidyl-m-aminophenol or triglycidyl-aminocresol and their isomers containing phenolic groups epoxy resins, such as epoxy resins based on bisphenol A, bisphenol P, bisphenol 8, phenolic novolach nozol, cresol novolac or resorcinol resins, as well as amicyclic epoxy resins. In addition, you can apply halogenated epoxy resins, glycidyl ethers of polyhydric phenols, diglycidyl ether of bisphenol A, glycidyl ethers of phenol-formaldehyde novolac resins and diglycidyl ether of resorcinol, as well as other epoxy resins, for example, described in US Pat. No. 3,018262 included in this application. links. These materials can be easily cured, or heat-cured, or cured by irradiation or by stitching.

Epoxy resins are particularly preferred in combination with metal particles, or metal oxides, or their combination as an agent that forms a network structure. In other embodiments, epoxy resins are preferred in combination with carbon and / or fullerene particles as an agent that forms a network structure.

According to some embodiments of the present invention, the matrix material does not contain cellulose or its derivatives, or it may be practically inelastic, or the matrix material contains almost no fibers or particles.

- 14 012091

The choice of matrix materials is not limited to the materials mentioned above, in particular, you can also use a mixture of epoxy resins based on two or more components, as described above, or you can use monoepoxides. Epoxy resins may also include resins that can be crosslinked by irradiation, for example, with UV light, and cycloaliphatic resins.

Other matrix materials include polyamides, for example aliphatic or aromatic polyamides and aramids (Neotech®), their derivatives, for example nylon-b- (polycaprolactam), nylon 6/6 (polyhexamethylene adipamide), nylon 6/10, nylon 6/12, nylon 6 / T (polyhexamethylene terephthalamide), nylon 7 (polyenantoamide), nylon 8 (polycaprilactan), nylon 9 (polypelargonamide), nylon 10, nylon 11, nylon 12, nylon 55, nylon ΧΌ6 (poly-xylylene adipamide), nylon 6/1 and polyalanine.

It is also possible to use phosphinates metals or phosphinates ores, as well as inorganic metal-containing polymers or organic metal-containing polymers such as, for example, metallodendrimery, metallocene polymers, carbosilane, polyynes, polymers alkynyl noble metals, polymers metalloporphyrins, metallotsenofany copolymers metallotsenilsilanov with carbosilane as mono -, diblock, triblock or multiblock copolymers, as well as poly (metallocenyldimethylsilanes), carbotium metallocenophanes, poly (carbothiamet allocene), etc., and this list of compounds is not exhaustive and may include any combination of these compounds.

In one embodiment, the matrix material may include electrically conducting polymers, such as saturated or unsaturated poliparafenilenvinilen, polyparaphenylene, polyaniline, polythiophene, poly (ethylenedioxythiophene) polidialkilfluoren, polyazine, polyfuran, polypyrrole, poliselenofen, poly-p-phenylene sulfide, polyacetylene, and monomers, oligomers or polymers, or any combination and mixture with other monomers, oligomers or polymers derived from the monomers mentioned. Conductive or semiconducting polymers may have electrical resistance between 10 ¹² and 10 ¹² Ohm-cm. Further examples include monomers, oligomers or polymers containing one or more organic radicals, for example alkyl or aryl radicals, etc., or inorganic radicals, such as silicon or germanium-containing, etc., or any mixtures thereof.

Polymers, including complex metal salts, can also serve as a matrix material. Such polymers typically contain an oxygen, nitrogen, sulfur, or halogen atom or carbon-carbon unsaturated bonds capable of forming complexes with metals. Without limitation, examples of such compounds include elastomers, such as polyurethane, rubber, adhesive polymers and thermoplastics. The metal salts constituting the complexes include transition metal salts, such as SiS1 _2, CuBr _2, SoS1 _2, ΖηΟ'Η ΝίΟ'Κ ReS1 ₂ ReVg ₂ ReVg ₃ Si1 ₂ ReS1 _3, PE1 PE1 ₂ or _3; salts such as Cu (IO ₃ ) ₂ , metal lactates, glutamates, succinates, tartrates, phosphates, oxalates, L1BP ₄ and H ₄ Fe (CH) _6, and the like.

According to some embodiments of the present invention, the matrix material can be biopolymers, biocompatible or biodegradable polymers such as collagen, albumin, gelatin, hyaluronic acid, starch, cellulose, for example methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose phthalate; casein, dextrans, polysaccharides, fibrinogen, poly- (O, L-lactide), copoly- (P, L-lactide-glycolides), polyglycolides, polyhydroxybutylates, polyalkyl carbonates, polyorthoesters, poly (hydroxyvaleric acid), polydioxanone, isocyanates, polyacrythols, polyacrythols, polytoxyethers, polyhydroxybuflate , polyvinyl acid, polyanhydrides, polyphosphazenes, polyamino acids or shellac.

In addition, the matrix material may be selected from oligomers or elastomers, such as polybutadiene, polyisobutylene, polyisoprene, poly (styrene-butadiene-styrene), polyurethanes, polychloroprene, silicone, and any mixtures, copolymers, and combinations thereof. The matrix material can also be selected from pH-sensitive polymers, such as, for example, polyacrylic acid and its derivatives, homopolymers such as poly (aminocarboxylic) acid, poly (methacrylic) acid, and copolymers of these compounds; or it can be selected from temperature sensitive polymers, such as, for example, poly- (H-isopropylacrylamide-Co-sodium-acrylate-Co-n-H-alkylacrylamide), poly- (C-methyl-N-n- propylacrylamide), poly- (N-methyl-N-isopropylacrylamide), poly- (N-n-propylmethacrylamide), poly- (N-isopropylacrylamide), poly (N-diethyl acrylamide), poly- (N-isopropylmethacrylamide), poly - (H-cyclopropylacrylamide), poly- (H-ethyl acrylamide), poly- (L-ethyl methacrylamide), poly- (L-methyl-H-ethyl acrylamide), poly- (L-cyclopropylacrylamide). In addition, suitable matrix materials are polymers with thermogel properties including hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, and pluronics (Pligox8®), such as P-127, L-122, L-92, L81, or L61.

The matrix material itself can be in liquid form, for example, it can be a liquid prepolymer, a polymer melt or solution, dispersion, emulsion, and can be mixed with at least one agent that forms a network structure in the absence or in the presence of a solvent, or matrices can be hard.

Liquid mixture.

- 15 012091

For the manufacture of a medical device, at least one reticulating agent is combined with the matrix material, possibly in the presence or absence of a suitable solvent or solvent mixture, to form a flowable mixture, for example, solution, suspension, dispersion or emulsion, or melt, pulp, paste or fluid mixture of particles. The liquid mixture may be substantially homogeneous and / or practically homogeneous. However, in most cases, the homogeneity or homogeneity of the liquid mixture is not critical.

Suitable solvents may include water, sols or gels, or non-polar or polar solvents, such as methanol, ethanol, n-propanol, isopropanol, butoxydiglycol, butoxyethanol, butoxyisopropanol, butoxypropanol, n-butyl alcohol, tert-butyl alcohol, tetras, butoxypropanol, n-butyl alcohol, tert-butyl alcohol, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras, tetras. diethylene dimetoksidiglikol, dimethyl ether, dipropylene glycol, ethoxydiglycol, ethoxyethanol, etilgeksandiol glycol, hexanediol, 1,2,6-hexanetriol, hexyl alcohol, hexylene glycol, izobutoksipropanol, izopentildiol, methyl ethyl ketone, toxipropylacetate, 3-methoxybutanol, methoxyglycol, methoxyethanol, methoxyisopropanol, methoxymethylbutanol, methoxy-PEO10, methylal, methylhexyl ether, methylpropane diol, neopentylglycol, PEO-4, PEO-6, PEO-7, PEO8-PE, REA-PE, 3-PE, 4 ether, pentylene glycol, PPO-7, PPO-2-butyl-3-ether, PPO-2-butyl ether, PPO-3-butyl ether, PPO-2-methyl ether, PPO-3-methyl ether, PPO-2- propyl ether, propanediol, propylene glycol, propylene glycol butyl ether, propylene glycol propyl ether, tetrahydrofuran, trimethylhexanol, phenol, benzene, toluene , xylene, each of which can be mixed with dispersants, surfactants and other additives, and mixtures of the above substances.

Easily removable solvents are sometimes preferred, these are solvents that easily evaporate. Examples may be solvents with a boiling point below 120 ° C, for example below 80 ° C or even below 50 ° C. The solvent or mixture of solvents can be used to facilitate the efficiency of dispersion of solid particles, especially in cases where homogeneous or homogeneous liquid mixtures are preferred.

The solvent used in some embodiments may also be selected from solvent mixtures that are suitable for dissolving or swelling the matrix material or at least a portion or main component of the matrix material if it is a mixture or composite. According to some embodiments of the invention, solvents are preferred which substantially dissolve the matrix material.

According to some embodiments of the invention, the liquid mixture may be in the form of a colloidal solution, solid solution, dispersion, suspension or emulsion, which contain at least one matrix material and at least one agent that forms a network structure.

The person skilled in the art can select the matrix material, the agent that forms the network structure, the solvent and possible additives in such a way as to obtain a practically stable and possibly homogeneous dispersion, suspension, emulsion or solution.

The dynamic viscosity of a liquid mixture containing a solvent, for example, a solution, dispersion, suspension or emulsion containing a matrix material and a network-forming agent, may be at least 10-99%, preferably 20-90% or 50-90% less than the viscosity of the matrix material at the temperature of application of the liquid mixture before curing, preferably at a temperature of about 25 ° C.

When the mixture capable of fluidity, does not contain a solvent, the temperature and / or composition of the liquid mixture or the matrix material can be chosen so that the dynamic viscosity of the mixture capable of fluidity and not containing solvent, was at least 10-99%, preferably 20-90% or 50-90% less than the viscosity of the matrix material at the specified temperature. These values refer to the mixture before crosslinking begins or prior to the addition of crosslinking agents, respectively. Viscosity can be measured by conventional methods, for example, in a Brookfield capillary viscometer.

In addition, the specific combination of agents that cause the formation of a mesh structure, a solvent and a matrix material can be chosen so that the selected agents that form the mesh structure are moistened with a solvent, a matrix material or a liquid mixture. You can modify the agents that form the mesh structure, using suitable additives and surface modifiers, as described above, to increase their wettability, preferably to achieve full wettability.

Further, at least one agent forming the network structure and the matrix material can be connected in a certain weight or volume relationship to each other, for example, in order to optimize the structure of porous composites obtained under the conditions of solidification of the liquid mixture. The specific ratio of both components may depend on the molecular weight, particle size and specific surface area of the particles. The ratio may be such that after removing the solvent in the curing step or after changing the viscosity of the matrix component, separation of the phases into a solvent and a solid phase consisting of the matrix material and the agent forming

- 16 012091 mesh structure. The change in viscosity can be achieved by changing the temperature in the direction of increasing or decreasing or by adding cross-linking agents, especially in systems that do not contain a solvent.

This phase separation facilitates the formation of a three-dimensional solid phase network, for example, by self-orienting the components used. According to some embodiments of the invention, the volume ratio between the total volume of agents forming the network structure and the total volume of the matrix material can vary from about 20:80 to 70:30, preferably from 30:70 to 60:40 or from 50:50 to 60:40 .

According to some embodiments of the invention, the solids content in the liquid mixture may be up to 90% by weight, calculated on the total weight of the liquid mixture, preferably up to 80%, or be less than 20% by weight based on the total weight of the liquid mixture, preferably less than 15%, for example, less than 10% or sometimes even less than 5 wt.%.

Supplements.

Using additives, you can further change and adjust the mechanical, optical and thermal properties of the material, which may be particularly suitable for obtaining coatings with desired properties. Therefore, in some embodiments of the invention, various additives may be added to the liquid mixture.

Examples of suitable additives include fillers, additional blowing agents, metals and metal powders, etc. Examples of inorganic additives and fillers include silica and alumina, aluminosilicates, zeolites, zirconium oxides, titanium oxides, talc, graphite, carbon black, fullerenes, clays, phyllosilicates, silicides, nitrides, metal powders, including transition metals such as copper, gold, silver, titanium, zirconium, hafnium, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium or platinum.

Other suitable additives can be crosslinkers, plasticizers, lubricants, flame retardants, glass or fiberglass, carbon fibers, cotton, fabrics, metal powders, metal compounds, silicon, silica, zeolites, titanium oxide, zirconium oxide, aluminum oxide, aluminum silicates , talc, graphite, carbon black, phyllosilicates, etc.

Typical additives for crosslinking include, for example, organosilanes, such as tetraalkoxysilanes, alkylalkoxysilanes, aryltrialkoxysilanes, for example, described above and in PCT / EP 2006/050622 and in US patent application number 11/346983, these compounds can also be used as crosslinkers agents according to embodiments of the invention.

If necessary, other additives may be added to wet the components, disperse and / or stabilize the components, or electrostatic stabilizers, thixotropy modifiers, such as various additives and dispersing agents sold under the Vuk®, Oksrhbuk® or Nrbybuk® brands from Vuk-Skepke StjH. Segtapu or equivalent formulations from other manufacturers.

Emulsifiers may be used in the liquid mixture. Suitable emulsifiers can be selected from anionic, cationic, zwitterionic or non-ionic surfactants, and any combinations thereof. Anionic surfactants include: fatty acid amido ester sulfates, mono- and dialkyl sulfosuccinates, mono- and dialkyl sulfosuccinates, sulfotriglycerides, amide soaps, ether carboxylic acid and their salts, fatty acid iso-ionates, arcosinates (atso1301) fatty acids, fatty acid taurides, α-acylamino acids, such as acyl lactylates, acyl tartrate, acyl glutamates and acyl aspartate; wheat and alkyl (ether) phosphates.

Cationic surfactants suitable for encapsulation according to some embodiments of the invention may include quaternary ammonium compounds such as dimetildistearilammoniyhlorid, Yb 81erap1eh® 90 (§1erap), quaternary esters, in particular salts trialkanolaminoefirov quaternized fatty acids, salts of long-chain primary amines, quaternary ammonium compounds such as hexadecyltrimethylammonium chloride (STMA-C1), EekutsiaP® A (cetrimonium chloride, Sodp18) or EekutsiaP® BIV 50 (lauryl dimethylbenzylammonium chloride, Sodp to).

The specialist can choose any or more of these additives when it is necessary to obtain a stable dispersion, suspension or emulsion in a liquid mixture.

In addition to the mesh forming agents, additional fillers can be used to modify the pore size and porosity degree. In some embodiments of the invention, non-polymeric fillers are preferred. Non-polymeric fillers include any substance that may be removed or decomposed, for example, by heat treatment, washing or

- 17 012091 other conditions, without deteriorating the properties of the material. Some fillers can be dissolved in a suitable solvent and thus removed from the resulting material. In addition, non-polymeric fillers can be used that can be converted to soluble substances under selected thermal conditions. Non-polymeric fillers include, for example, anionic, cationic and non-ionic surfactants, which can be removed or decomposed, for example, under selected thermal conditions. Fillers may also include inorganic metal salts, in particular alkali and / or alkaline earth metal salts, such as carbonates, sulfates, sulfites, nitrates, nitrites, phosphates, phosphites, halides, sulfides, and oxides of alkali and alkaline earth metals.

Other suitable fillers include organic metal salts, for example alkali or alkaline earth and / or transition metals, for example, their formates, acetates, propionates, malates, maleates, oxalates, terrates, citrates, benzoates, salicylates, phthalates, stearates, phenates, sulfonates , salts of amines, as well as their mixtures.

Alternatively, polymeric fillers can be used. Suitable polymeric fillers can be polymers, referred to as polymers for encapsulation, especially in the form of spheres or capsules. Preferred examples include polymers of saturated linear or branched hydrocarbons, which may be homo- or copolymers, for example polyolefins, such as polyethylene, polypropylene, polybutene, polyisobutene, polypentene, as well as their copolymers and mixtures. In addition, polymeric particles based on methacrylates or polystyarin can be used as polymer fillers, for example, to obtain electrically conductive polymers, as well as electrically conductive polymers described above, such as, for example, polyacetylenes, polyanilines, poly (ethylenedioxythiophenes), polydialkylfluorenes, polythiophenes or polypyrroles.

Soluble fillers and polymeric fillers that are volatile under the thermal conditions used, for example, at the curing step of the invention, or which can be converted into volatile compounds during heat treatment, can be combined. Thus, the pores formed by polymeric fillers are combined with pores formed by agents that form a network structure or other fillers to achieve an isotropic or anisotropic distribution of pores, for example, a hierarchical pore size distribution.

A suitable particle size of the non-polymeric fillers can be determined by a person skilled in the art depending on the desired porosity and / or pore size of the composite material obtained. Suitable solvents that can be used to remove fillers or at the purification stages after curing the material include, for example, (hot) water, diluted or concentrated inorganic or organic acids, bases, or any of the solvents described in this application. Suitable inorganic acids include, for example, hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, as well as dilute hydrofluoric acid. Suitable bases include, for example, sodium hydroxide, ammonia, carbonate, as well as organic amines. Suitable organic acids include, for example, formic acid, acetic acid, trifluoromethanesulfonic acid, trichloromethanesulfonic acid, citric acid, tartaric acid, oxalic acid, and mixtures thereof.

Fillers can be partially or completely removed from the mesh composite material, depending on the nature and time of processing solvent. Complete removal of the filler after curing is preferred.

Cure.

The curing step usually depends on the properties and composition of the liquid mixture. Curing can be accomplished, for example, by heat treatment, for example heating or cooling; by changing the pressure, such as vacuuming, flushing or ventilating, drying with gases, including inert gases, drying by freezing, drying by spraying, filtering or chemical or physical curing or hardening, for example, combined with thermal sewing or irradiation with the aim of stitching or by applying any combination of these techniques.

Preferably, when curing practically takes place without decomposition of the matrix material or a combination of at least one agent forming the network structure and the matrix material, i.e. when there is practically no thermolysis or pyrolysis of the matrix material. The agents forming the network structure can be embedded in the matrix material.

The person skilled in the art can select suitable conditions, such as temperature, medium or pressure, depending on the desired properties of the final composite material according to the invention and the components used, in order to accomplish almost complete curing.

According to preferred embodiments of the present invention, the curing step may include separating the phases of the liquid mixture into a solid phase and a liquid phase, for example, by precipitating solid particles from the liquid mixture. Without being limited to any particular theory, it is believed that such phase separation or precipitation facilitates or even accelerates the development of the network structure in the resulting composite material. Such a development of the structure may preferably occur before the solution is removed.

- 18 012091 bodies, for example, phase separation or precipitation may occur before removing at least one solvent.

In the preferred stages of some embodiments of the invention, phase separation or precipitation is induced by at least one method, including removal of solvent (s), crosslinking of the matrix material or increase in the viscosity of the liquid mixture.

Increasing the viscosity of a liquid mixture can be triggered by at least one method, including cross-linking, curing, drying, a rapid temperature increase, a rapid decrease in temperature, or a rapid removal of solvent. The term rapid in this context means that it takes less than 5 hours, preferably less than 1 hour, or less than 30, 20, 15, 10, 5 minutes, or even less than 2 minutes, or less than 1 minute after the start, to perform the procedure indicated above. . The time required for this usually depends on the mass of the liquid mixture.

Heat treatment may include heating or cooling in the temperature range from -78 to 500 ° C and may include heating or drying during freezing, etc.

The solvent can be removed from the liquid mixture prior to heat treatment. This can be achieved by filtration or usually by heat treatment of the liquid mixture, for example cooling or heating, in the range of temperatures from about -200 to 300 ° C, for example in the range of from about -100 to 200 ° C or in the range of from about -50 to 150 ° C, including from about 0 to 100 ° C or from about 50 to 80 ° C. You can also use solvent evaporation at room temperature or in a stream of hot air or other gases. Drying can be carried out by spraying, freezing, or similar conventional methods.

Curing may also include heating at elevated temperatures with or without prior removal of the solvent, usually at a temperature of from about 20 to about 4000 ° C, or from about 100 to about 3500 ° C, or from about 100 to about 2000 ° C, for example from about 150 to about 500 ° C, possibly under reduced pressure or under vacuum, or in the presence of inert or reactive gases.

Curing without decomposition of any of the components can be carried out at temperatures up to about 500 ° C, however, in some embodiments of the present invention, it may be preferable to partially or completely carbonize, pyrolyze or decompose one of the components of the composite material during or after curing. This is usually done at higher temperatures from about 150 to about 4000 ° C. These high temperatures may also be used according to some embodiments of the invention, when an additional sintering step may be desirable.

However, usually the sintering stages at high temperatures, namely at temperatures above 500 ° C., are not needed, and the processing steps, including decomposition of the substance, i.e. pyrolysis or carbonation, are preferably not carried out. The curing step of some embodiments of the invention uses temperatures ranging from about 20 to 500 ° C, for example, from about 30 to 350 ° C, including from about 40 to 300 ° C or below 200 ° C, for example, from about 100 to 190 ° WITH.

The curing step can be carried out in a different medium, for example in an inert atmosphere, such as nitrogen, 8P ₆ or noble gases, such as argon, or any mixtures thereof, or in an oxidizing medium containing, for example, oxygen, carbon monoxide, carbon dioxide or oxide nitrogen. In addition, the inert atmosphere can be mixed with reactive gases, such as hydrogen, ammonia, C ₁ -Cb, saturated aliphatic hydrocarbons, such as methane, ethane, propane and butane, and their mixtures.

According to some embodiments of the invention, the medium at the stage of curing, especially in the case of heat treatment of the liquid mixture, can be oxidizing, for example, air, oxygen or oxygen-enriched inert gases. Alternatively, the medium at the stage of curing may essentially not contain oxygen, that is, the oxygen content may be less than 10 ppm or even less than 1 ppm.

Curing can also be carried out using a laser, for example, during sintering under the action of selective laser radiation (Sb8), or under the action of radiation, for example, using UV-crosslinking agents or gamma-rays.

It may be preferable to precipitate solid components from the solvent-based liquid mixture, for example, by heat treatment, crosslinking or evaporation of the solvent. For the formation of, for example, a substantially homogeneous porous structure in the resulting composite material and / or to accelerate the formation of a reticular structure when the particles are oriented in a liquid mixture, low viscosity is preferred, as well as, for example, a rapid increase in the viscosity of the solid phase during curing. This can be achieved by separating the solid phase from the solvent phase. When performing this operation, the applied temperature usually depends on the freezing point or boiling point of the solvent, respectively, and the matrix material.

The solvent in the case of curing with increasing temperature may have a boiling point of from at least about 5 to about 200 ° C, for example from about 30 to 200 ° C or from about 40

- 19 012091 to about 100 ° C below the melting point of the matrix material, while there is no significant reduction in the viscosity of the matrix material, melting or incomplete thermal decomposition of the matrix material or agents forming a network structure during the heat treatment of the liquid mixture and / or during removal solvent.

In a preferred embodiment of the invention, the liquid mixture hardens with a rapid, instantaneous decrease in temperature. This can be carried out with liquid mixtures containing or not containing solvent. In a mixture with a solvent, the solvent may have a boiling point that is at least 10-100 ° C, preferably 20-100 ° C and particularly preferably 30-60 ° C above the melting point of the matrix material.

Upon receipt of a dispersion, suspension, emulsion or solution at temperatures near the melting point of the matrix material, preferably a polymer, a network of agents forming a network can form, with a rapid decrease in temperature resulting in a rapid increase in the viscosity of the liquid mixture. For the introduction of the agents that form the net structure into the matrix material, the solvent can be removed from the liquid mixture under vacuum.

In the dispersion, suspension or emulsion, forming a liquid mixture, crosslinking agents may be added. Cross-linking agents may include, for example, isocyanates, silanes, diols, dicarboxylic acids, (meth) acrylates, such as, for example, 2-hydroxyethyl methacrylate, propyl trimethoxysilane, 3- (trimethylsilyl) propyl methacrylate, isophorone diisocyanate, polyols, glycerol, and the like. Biocompatible crosslinkers, such as glycerin, diethylenetriaminoisocyanate and 1,6-diisocyanathexane, may be preferred, for example, when the liquid mixture turns into a solid composite material at fairly low temperatures, for example, below 100 ° C.

The amount and type of crosslinking agent can be chosen in such a way that crosslinking during the curing of the liquid mixture does not lead to a significant change in the viscosity of the system before the formation of a solid phase of the composite during phase separation or solvent evaporation. Crosslinking can be interrupted and components of the matrix material that are not yet crosslinked or not fully crosslinked can be dissolved and removed when processing the system with suitable solvents in order to modify the morphology and the entire structure of the composite material.

Subsequent processing.

The liquid mixture or the final composite material can then be processed by several methods, depending on the intended application.

For example, a reductive or oxidative treatment step can be carried out when the hardened material or coating is treated one or more times with suitable reducing agents or oxidizing agents such as hydrogen, carbon dioxide, water vapor, oxygen, air, nitrous oxide or oxidizing acids such as nitric acid and etc., and possible mixtures thereof, to modify pore size and surface properties. Air activation is one of the options and is carried out, for example, at elevated temperatures, such as from about 40 to 1000 ° C, from about 70 to 900 ° C or from about 100 to 850 ° C, sometimes from about 200 to 800 ° C or at about 700 ° C. The composite material can be modified by reduction or oxidation, or a combination of these treatments at room temperature. For modification of surface and bulk properties, when this is desired, boiling in oxidizing acids or bases can be used.

The pore size and pore structure can vary according to the type of oxidizing agent or reducing agent, temperature and duration of activation. The porosity can be adjusted by washing out the fillers that are contained in the composite material, as described above. These fillers may include polyvinylpyrrolidone, polyethylene glycol, aluminum powder, fatty acids, microviox or emulsions, paraffins, carbonates, dissolved gases or water-soluble salts that can be removed with water, solvents, acids or bases or by distillation or oxidative and / or non-oxidative thermal decomposition . Such methods are described, for example, in patent No. 10322187 and / or in international application PCT / EP 2004/005277 and can be applied according to the invention.

Material properties can also be changed by structuring the surface with powdered substances such as metal powder, carbon black, phenolic resin powder, fibers, in particular carbon fibers or natural fibers.

Composite material can also be processed by the so-called method of EMS (chemical vapor deposition) or method SU1 (chemical impregnation with vapor) at another possible stage of the process in order to further modify the surface structure or pore structure and material properties. For this, the material or coating can be treated with a suitable precursor of gases that emit carbon at high temperatures. The subsequent deposition of diamond-like carbon is preferred. Other elements, such as silicon, can also be precipitated by conventional methods. As precursors emitting carbon, it is possible to use almost all known saturated and unsaturated hydrocarbons that have sufficient volatility under the conditions of the EMS. Suitable ceramic precursors include, for example, BC1 ₃ , ΝΗ ₃ , silanes, such as δίΗ ₄ , tetraethoxysilane (ΤΕΘ8), dichlorodimethylsilane (8), methyltrichlorosilane (MT8), trichloroxy

- 20 012091 lildichlorborane (ΤΟΑΟΒ), hexadichloromethylsilyloxide (80), A1C1 ₃ , T1C1 _3, and mixtures thereof. Using the MSA method, the pore size in a material can be reduced in a controlled manner, or the pores can even be completely closed and / or sealed. This allows you to adjust the sorption properties, as well as the mechanical properties of the composite material in a given way. Using the MSF method of silanes or siloxanes, possibly in a mixture with hydrocarbons, the materials or coatings can be modified by the formation of carbide or oxycarbide in such a way that they become, for example, resistant to oxidation.

The materials and devices obtained according to the invention can be further coated or modified by sputtering or ion implantation / ion bombardment. Carbon, silicon and metals or metal compounds can be applied by conventional methods using suitable sprayers. For example, by introducing silicon compounds, titanium compounds, zirconium compounds, or tantalum compounds or metals by means of an OMS or RBM material, carbide phases can be formed which increase the stability and resistance to oxidation.

The composite materials described in this application may have an average pore size of at least 1 nm, preferably at least 5 nm, more preferably at least 10 nm or at least 100 nm, or from about 1 nm to about 400 microns, preferably from 1 nm to 80 μm, more preferably from 1 nm to about 40 μm, or in the macroporous region from about 500 nm to about 1000 μm, preferably from 500 nm to about 800 μm, or from 500 nm to about 500 μm, or from 500 nm to about 80 microns, and average porosity from about 30 to ERNO 80%.

In addition, the composite material can be machined to obtain a porous surface. For example, controlled grinding of the surface layer (s) by suitable methods can result in modified porous surface layers. You can clean and grind in an ultrasonic bath, where you can get defects in the material and additional pores using a mixture of hard abrasives with particles of different sizes and degrees of hardness, changing the amount of energy and frequency of ultrasonic vibrations depending on the processing time. Aqueous ultrasonic baths are used, in which alumina, silicates, aluminates, and the like are added, preferably dispersions of alumina. However, instead of water or with it, you can use any other solvent suitable for ultrasonic baths.

The surface properties of the material can also be modified by implanting metal ions, in particular transition metal ions and non-metal ions. For example, by implanting nitrogen, nitrides, oxynitrides or carbonitrides can be obtained, in particular, such transition metal compounds. The porosity and surface strength of materials can be modified by carbon implantation.

Composite network materials can also be modified, for example, by applying biodegradable and / or resorbable or non-biodegradable and / or resorbable polymers, possibly porous, for example, in the form of layers or surface coating.

In addition, it is also possible to modify the surface properties and porosity of the material by deprotecting composite mesh materials before or after any stage of activation. Materials are first treated with p-cyclophane at elevated temperatures, usually around 600 ° C, using a poly (p-xylylene) polymer film formed on the surface of the material. This film can then, for example, be turned into carbon by known methods in the subsequent carbonization step.

If necessary, the mesh material can be subjected to additional chemical and / or physical surface modification. Cleaning steps can also be carried out to remove any residues and impurities. Acids may be used for this purpose, in particular oxidizing acids, or solvents, but boiling in acids or solvents is preferable. By boiling in oxidizing acids, one can achieve carboxylation of some materials. For further processing of crosslinked materials / devices, it is also possible to use washing with organic solvents, possibly using ultrasound and optionally at elevated temperatures.

Crosslinked materials / devices can be sterilized by conventional methods, for example, in an autoclave, in an ethylene oxide environment, under pressure or under the action of gamma radiation. According to the invention, all these steps can be combined and applied in combination with each other or with the steps described below.

Coatings or bulk porous mesh materials, either by themselves or applied to the device, can be structured by a suitable method before or after curing to obtain a composite material according to the invention using folding, profiling, punching, pressing, extrusion, assembly, injection molding, etc. . before or after application to the substrate or can be molded or formed. By this method, in a composite coating obtained from a material according to the invention, it is possible to introduce some structures of regular or irregular shape.

The mesh material can then be processed by standard methods to obtain the desired shape or at least part of it, for example, by assembling molded packing mats.

- 21 012091 riyals, etc. or by obtaining coatings on any medical device.

Composite materials can be obtained in any desired form. Asymmetrical structures can be obtained from these materials using multilayer molded blanks. Materials can be given any shape using any standard methods including, but not limited to, casting, such as sand casting, shell casting, injection molding, centrifugal casting, or pressing, sintering, injection molding, direct pressing, molding with blow molding, extrusion, calendering, fusion welding, pressure welding, mandrel assembly, slip casting, dry pressing, drying, firing, winding, pull-outs, laminating, autoclaving, curing or braiding.

Composite mesh-based coatings can be applied in a liquid, paste-like form and as a slurry, for example, by applying a paint coating, filling, phase inversion, pulverization or melt coating, extrusion, die casting, slip casting, dipping or hot melt, for example, directly from the liquid mixture prior to curing. When the material is already in a solid state, it can be applied to a suitable substrate by powder spraying, flame spraying, sintering in order to obtain a medical device. Dipping, spraying, centrifuging, inkjet printing, rubbing coating, microdroplet coating or 3-E printing are preferred when applying the liquid mixture to the substrate. The application of the liquid mixture can be carried out using a high-frequency spraying device, as described, for example, in the international application of applicants PCT / EP 2005/000041, or by printing or roller application, using the device described in the international application of applicants XVO 2005/042045. These devices and methods can be used to further apply coatings to a medical device based on any other agents, for example, therapeutically or diagnostically active or additional coatings, as described below. A coating based on a net material can be obtained, for example, by applying a liquid mixture to a medical device, drying and, if necessary, heat treating.

In addition, coated devices can be obtained by a transfer method when the mesh material is applied to the substrate in the form of a finished laminate. Devices with coatings can be dried, cured and then the coating can be treated, for example, thermally. A coated medical device can also be obtained by suitable printing methods, such as intaglio printing, enamel overflow, and doctoring, spraying or thermal lamination or wet-wrap layering. You can apply more than one layer, for example, in order to obtain a defect-free film of a composite material. Using the above transfer process, it is possible to form multilayer gradient films from different layers with different sequence of layers, which, after curing, results in gradient materials in which the density of the net material changes from place to place.

The liquid mixture can also be dried or thermally treated and then crushed by conventional methods, for example by grinding in a ball mill or in a roller mill, etc. The crushed net material can be applied in the form of powder, slab, rod, spheres, hollow spheres of various sizes and can be processed by conventional methods into granulates or extrudates of various shapes. To obtain a medical device or parts of it from a net material, it is possible to apply methods of pressing with heating, if necessary, using suitable binders.

Other processing options are the production of powders by other conventional methods, for example, pyrolysis of a spray layer or the deposition or spinning of fibers by spinning, for example centrifugal spinning.

Functionalization and application.

With an appropriate choice of components and conditions for obtaining described in this application, the methods allow, for example, to obtain biodegradable or biodegradable materials, devices or coatings or coatings and mesh materials that are soluble and can be peeled off from the substrate in the presence of, for example, physiological fluids. For example, coatings that can be used in the field of medicine for coronary implants, such as stents, can be obtained, and the coating may contain a therapeutically and / or diagnostically active agent.

Therapeutically and / or diagnostically active agent may be incorporated into the composite material as at least part of the network forming agent, matrix material, as an additive, or it may be introduced onto the surface or into the composite network material after curing.

The diagnostically active agent can be a marker, a contrast medium, or a material that is not transparent to radiation and that generates a signal that can be detected by physical, chemical, or biological detection methods. The terms diagnostically active agent, diagnostic agent and marker are used interchangeably. Examples of such materials are mentioned in part in the section on agents that form the grid, and other suitable diagnostic agents with the property to generate signals are described in detail in the accompanying application of US patent applicants No. 11/322694 and

- 22 012091 international application PCT / EP 2005/013732 and can be used according to the invention as markers. Some matrix materials can also form signals and therefore can serve as markers or a contrast medium. Composite cross-linked material can be properly modified to provide controlled release of the diagnostic agent.

Coatings that can be applied to coronary implants, such as stents, can be made as described in this application, and the coating contains an encapsulated marker, such as a metal compound, that has signal-forming properties, that is, which generates signals that can be detected by physical, chemical or biological detection methods such as x-ray, nuclear magnetic resonance (NMR), computed tomography, scintigraphy, single-proton emission computed tomography (8REST), ultrasound research, radio frequency method (KE), etc. For example, metal-based agents that form a mesh structure, used as markers, can be encapsulated in a polymer shell and thus do not act on a medical device, for example, on an implant material, often also a metal, which could otherwise result in electro-corrosion or her problems. Coated implants can be made with encapsulated markers, while the coating is permanently on the implant. According to one embodiment of the present invention, the coating can quickly dissolve or peel off from the surface of the stent after implantation under physiological conditions, which allows temporary marking.

If used therapeutically active agents that form the grid, they can be encapsulated in biodegradable or resorbable materials, which provides a controlled release of the active ingredient under physiological conditions. It is also possible to obtain coatings or composite materials into which, by a given porosity, therapeutically active agents can be introduced, which can be dissolved or extracted in the presence of physiological fluids. This allows, for example, to obtain medical devices or implants that provide controlled release of active agents. Examples include drug-eluting stents, drug delivery implants, orthopedic implants, drug-releasing, etc.

In addition, the methods described here can be used to make porous bone and tissue implants, possibly with coatings (destructible and non-destructible), porous implants, possibly with coatings, and joint implants, as well as porous trauma devices, such as nails, screws or plates for example, with improved implantability and therapeutic functionality, with radiating ability, for example, for local radiotherapy of tissues and organs.

Other mesh material and / or coating based on it may contain conductive fibers, for example, nanotubes, which have good reflective and absorbing properties with respect to electromagnetic radiation and therefore can protect, for example, electronic medical devices, such as metal implants or pacemakers and their parts.

You can also get porous mesh materials based on carbon tubes and nanofibers with high specific surface and specific thermal and anisotropic electrical conductivity, which can be used for drives in the micro- and macro-regions, as well as thin film materials for the manufacture of artificial muscles or excitatory fibers and films.

Further, medical devices can be loaded with active ingredients. The active ingredients can be introduced into the porous composite material or on its surface by suitable sorption methods, such as adsorption, absorption, physical sorption or chemical sorption; in the simplest case, they can be loaded by impregnating a medical device with solutions of active ingredients, dispersions of active ingredients or suspensions of active ingredients in suitable solvents. It is preferable to bind the active ingredients with the medical device covalently or non-covalently depending on the active ingredient used and its chemical properties.

Active agents can be biologically and / or therapeutically active agents, as well as active agents for diagnostic purposes, all of which are referred to as active agents. Such active agents include therapeutically active agents that are capable of providing direct or indirect therapeutic, physiological and / or pharmacological action in the human or animal body. A therapeutically active agent may be a drug, a prodrug, or even a target group or a drug containing an target group.

The active agents may be in crystalline, polymorphic, or amorphous form, or any combination thereof. Examples of therapeutic agents include enzyme inhibitors, hormones, cytokines, growth factors, receptor ligands, antibodies, antigens, ion-binding agents such as crown ethers and chelating compounds, complementary nucleic acids, nucleic acid binding proteins, including transcription factors, toxins etc.

Other examples of active agents used in accordance with embodiments of the present invention may be active agents, therapeutically active agents, and drugs described in International

- 23 012091 application PCT / EP 2006/050622 and in US patent application number 11/346983.

Suitable therapeutically active agents may include, for example, enzyme inhibitors, hormones, cytokines, growth factors, receptor ligands, antibodies, antigens, agents that bind ions, such as crown ethers and chelating compounds, complementary nucleic acids, nucleic acid binding proteins, including transcription factors, toxins, etc.

Examples of active agents include, for example, cytokines, such as erythropoietin (EPO), thrombopoietin (TPO), interleukins (including 16-1-16-17). insulin, insulin-like growth factors (including YR-1 and YR-2), epidermal growth factor (ECP), transforming growth factors (including TCP-α and TCP-β), human growth hormone, transferrin, low-density lipoproteins, high-density lipoproteins , leptin, UESR, ROSR, ciliary neurotrophic factor, prolactin, adrenocorticotropic hormone (ACTH), calcitonin, human chorionic gonadotropin, cortisol, estradiol, follicle-stimulating hormone (R8N) tiroidstimuliruyuschy hormone (T8N), luteinizing hormone (LH), progesterone, dough theron toxins include ricin, other active agents such as those described in RbukShai'k Eekk KeGegeise 58 ^4b Εάίΐίοη, Meb1sa1 Esoiot1sk Ea1a rtobisboi Sotrapu, My! ua1e, Ν.Υ., 2004 and Merck 1ibeh, 13 ^'1' Ebyyui , including those listed on the pages Tbeg-1 - Tbeg-29.

According to a preferred embodiment of the invention, the therapeutically active agent may be selected from the group of drugs used to treat cancer and cell or tissue changes. Suitable therapeutic agents may include, for example, antineoplastic agents, including alkylating agents, such as alkyl sulfonates, such as busulfan, improsulfan, piposulfan, aziridines, such as benzodep, carboquone, meturedepa, urepepa; ethyleneimine and methylmelamines, such as altretamine, triethylenemelamine, triethylene, phosphoramide, triethylene thiophosphoramide, trimethylolmelamine; the so-called mustines, such as chlorambucil, chlornafazine, cyclophosphamide, extramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembicin, phenesterol, prednumustine, trofosfamide, uracilumustine; nitrosoureas, such as carmustine, chlorozotocin, photenmustine, lomustine, nimustine, ranimustine, dacarbazine, mannomustine, mitobranitol, mitolactol; pipobroman; doxorubicin and cis-platin and its derivatives, etc., as well as combinations and derivatives of any of these compounds.

According to another embodiment of the present invention, the therapeutically active agent may be selected from the group comprising antiviral and antibacterial agents, such as aclacinomycin, actinomycin, anthramycin, azaserin, bleomycin, cookinomycin, carubicin, carcinophyllin, chromomycin, ductinomycin, daunorubicin 6, i-dacin, 6 chromomycin, ductinomycin, 6-chrominyl, carcinophilin, chromomycin, ductinomycin, daunorubicin, 6-chrominomycin, carcinophilin, chromomycin, ductinomycin. hydroxy-1-noricin, doxorubicin, epirubicin, mitomycin, mycophenolic acid, mogbalamycin, olivomycin, peplomycin, plicamycin, porfiromycin, puromycin, streptonigrin, streptozocin, tubercidin, ubinimex, zinostatin, zorubicin, aminoglycosides or polyenes or macrolide antibiotics, and the like, as well as combinations and / or derivatives of any of these compounds.

According to another embodiment of the invention, the therapeutically active agent may include X-ray sensitive drugs, steroid and non-steroidal anti-inflammatory drugs or agents related to angiogenesis, such as, for example, endostatin, angiostatin, interferons, platelet factor 4 (PP4), thrombospondin, transforming growth factor beta, tissue inhibitors of metalloproteinases-1, -2 and -3 (T1MR-1, -2 and -3), T№-470, marimastat, neovastat, VM8-275291, COH-3, AC 3340, thalidomide, squalamine, combrestatatin, 8I 5416, 8I 6668, ΙΡΝ- [α], EMO 121974, CA1, 1b-12 and 1M 8 62, etc., as well as combinations and / or derivatives of any of these compounds.

According to another embodiment of the present invention, the therapeutically active agent may be selected from the group comprising nucleic acids, where the term nucleic acids includes oligonucleotides in which at least two nucleotides can be covalently linked together, for example, to provide for gene therapeutic or antisense effects . Nucleic acids may contain phosphodiester bonds, which may include analogs having different main chains. Analogs can also contain main chains, such as, for example, phosphoramid chains, as described, for example, Beaisade e! A1., Tebabebtoi 49 (10): 1925 (1993) and the references mentioned in this article; Le! Ctdet, 1. Sep. Sbet. 35: 3800 (1970); 8rpih1 e! A1., EIG. 1. Vusbet. 81: 579 (1977); Bе ktdeg e! A1., NR1. As1bk Keck. 14: 3487 (1986); 8a \\ sh! A1., Sbet. Ебeb. 805 (1984), le! A1., 1. At. Sbet. 8os 110: 4470 (1988); Aib Rai \\\ 'e1k e! a1., Sbetua 8sbr.a 26: 141 (1986); phosphorotioate, as described, for example, Mad e! A1., М.1с1е1с Ac1bk Kek. 19: 1437 (1991); and in US patent No. 5644048; phosphorodithioate, as described, for example, Vbi e! A1., 1. At. Sbet. 8os 111: 2321 (1989); O-methylphosphoramide (see, for example, Eskks., Oydoiislebekbek aib Aia1odk: A Rgasbs1 Arrghoisb, OhGogh Ishuetkyu Rgekk) and peptide-nucleic acid chains and their compounds, as described, for example, Edbo1t, 1. At. Sbet. 8os 114: 1895 (1992); Me ee! A1., Sbet. 1i !. Fuck Eid 1: 31: 1008 (1992); Nickle, Ia!, 365: 566 (1993); Sag1kkoi e! A1., No. 11IGE 380: 207 (1996). Other analogs may include compounds having ionic backbones, as described, for example, Euirsu e! a1., proc. No. Asab. 8c1. I8A 92: 6097 (1995), or non-ionic chains, as described, for example, in US Pat. Nos. 5,386,023, 5,637,684, 5,602,240, 5,216,141 and 4,469,863; K1ebgo \ uk1i e! A1., Aidete. Sbet. 1i! 1. Fuck Eidbkb 30: 423 (1991); Be! A1., 1. At. Sbet. 8os 110: 4470

- 24 012091 (1988); Bkshdeg e! A1., Shskombe & №1с1еоббе 13: 1597 (1994); Scargate 2 2 apb 3, A8C 8 utr§pc 8pe5 580, Sagokokbga1e Mobsabs η An! capge Keseagsk, Eb. Υ. 8. Graduate App R. Eap Sook; Meztaekeg e! A1., Vuogdats & Mebkt1 Sket. Ебeb. 4: 395 (1994); 1еШ е! a1., i.i bilocene 34: 17 (1994); Te! Hakebgop Lek. 37: 743 (1996) and non-fungal backbones, as described in U.S. Patent Nos. 5,235,033 and 5,034,506 and Chapters 6 and 7 of A8C 8froot 8 8g1e 5 580, Sagocoubga! E Mobsabs Ap! Υ. 8. Graduate App R. Oap Sook. Nucleic acids containing one or more carbocyclic sugars can also be acceptable for use according to some embodiments of the invention, for example, as described in Step 1! a1., Skeleton1 Sosteer et al. (1995), Radze 169-176 Appb Katek, C & E Teti, 2, 1997, Rade 36. In addition to the usual nucleic acids and nucleic acid analogues, you can also use mixtures of nucleic natural acids and nucleic acid analogs or mixtures of nucleic acid analogs.

According to another embodiment of the present invention, the therapeutically active agent may comprise one or more complexes of metal ions, such as those described in international applications PCT / I8 95/16377, PCT / I8 96/19900 and PCT / I8 96/15527, with such agents restore or inactivate the bioactivity of their target molecules, including proteins, enzymes.

Therapeutically active agents can be anti-depleting, anti-proliferative or immunosuppressive agents, anti-inflam-tases, and other subjects, such as everolimus, tacrolimus, sirolimus, mycophenolate-mofetil, rapamycin, paclitaxel, actinomycin, angiopoylethystine, actinomycin, angioteptine, mofetil, rapamycin, paclitaxel, actinomycin, angioprotectin, mycophenolate mofetil, rapamycin, paclitaxel, actinomycin, anci. p., as well as their derivatives and analogues.

Other active agents or components of active agents may include, for example, heparin, synthetic heparin analogs (for example, fondaparinux), hirudin, antithrombin III, drothrecogin alpha; fibrinolytics, such as ateplase, plasmin, mesokinase, factor X11a, prourokinase, urokinase, anistreplaza, streptokinase; platelet aggregation inhibitors, such as acetylsalicylic acid (i.e., aspirin), ticlopidine, clopidogrel, abciximab, dextrans; cortisol of the moon prednisone prednisone triamcinolone; so-called non-steroids, such as diclofenac celecoxib, rofecoxib; cytostatics, such as alkaloids and podophyllic toxins, such as vinblastine, vincristine; alkylating agents such as nitrosoureas, analogs that have lost the nitrogen atom; cytotoxic antibiotics such as daunorubicin, doxorubicin and other anthracyclines and related compounds, bleomycin, mitomycin; antimetabolites such as folic acid analogs, purine analogs or pyrimidine analogs; Paclitaxel, docetaxel, sirolimus; platinum compounds such as carboplatin, cisplatin or oxaliplatin; amsacrine, irinotecan, imatinib, topotecan, interferon-a-2a, interferon-a-2b, hydroxycarbamide, miltefosin, pentostatin, porfimer, aldesleukin, beksaroten, tretinoin; antiandrogens and antiestrogens; antiarrhythmic agents, in particular class I compounds, such as quinidine type antiarrhythmic agents, quinidine, disopyramide, aymalin, primalia bitartrate, detimemia bitartrate; lidocaine-type antiarrhythmic agents, for example, lidocaine, mexiletin, phenytoin, toacainide; class K antiarrhythmics, such as propafenone, flecainide (acetate); beta-receptor blockers of class II antiarrhythmic drugs, such as metoprolol, esmolol, propranolol, metoprolol, atenolol, oxprenolol; Class III antiarrhythmic drugs such as amiodarone, sotalol; class IV antiarrhythmic drugs such as diltiazem, verapamil, gallopamil; other antiarrhythmic drugs such as adenosine, ortsiprenalin, ipratropium bromide; agents for stimulating angiogenesis in the myocardium, such as vascular endothelial growth factor (WESE), basic fibroblastic growth factor (HECE), non-viral DNA, viral DNA, endothelial growth factors: ECE-1, ECE-2, WEC, TCE; antibiotics, monoclonal antibodies, antikalin; stem cells, endothelial progenitor cells (EPC); digitalis glycosides, such as acetyldigoxin / methyldigoxin, digitoxin, digoxin; cardiac glycosides such as ouabain, proscillaridin; antihypertensive drugs such as antiadrenergic agents active against the CNS, for example, methyldopa, imidazoline receptor agonists; calcium channel blockers of the dihydropyridine type, such as nifedipine, nitrendipine; ACE inhibitors: hinaprilat, cilazapril, moexipril, trandolapril, spirapril, imidapril, trandolapril; angiotensin II antagonists: candesartan cilexetil, valsartan, telmisartan, olmesartan-meduksomil, eprosartan, peripherally active α-receptor blockers such as prazosin, urapidil, doxazosin, bunazosin, terazosin, indoramine; vasodilators, such as dihydralazine, diisoprotelamine dichloroacetate, minoxidil, sodium nitroprusside; other antihypertensive drugs, such as indapamide, codergocrine mesilate, dihydroergoxin methanesulfonate, cyclanin, bosentan, fludrocortisone; phosphodiesterase inhibitors such as milrinone, enoximone and pressure-enhancing agents such as especially adrenergic and dopaminerg

- 25 012091 Ces substances such as dobutamine, epinephrine, ethylephrine, norfenephrine, norepinephrine, oxylophrine, dopamine, midodrin, folledrin, amesinium methyl; and partial adrenoreceptor agonists, such as dihydroergotamine; fibronectin, polylysine, ethylene-vinyl acetate, inflammatory cytokines, such as TSRZ, ROSE. USP, LPCP, THRK. ICCP, CM-C8P,-α, 1b-1, 1b-8, 1b-6, growth hormone; as well as adhesive substances such as cyanoacrylates, beryllium, silicon dioxide; and growth factors, such as erythropoietin, hormones, such as corticotropins, gonadotropins, somatropins, zircons, thyrotropins, desmopressin, terpressin, psitocin, cetrorelix, corticorelin, leprorelin, corticorelin as somatostatin, octreotide; peptides that stimulate the formation of bone and cartilage tissues, bone morphogenetic proteins (BMR3), especially recombinant BMR3, such as recombinant human BMP-2 (g11 BMP-2), bisphosphonate (for example, risedronate, pamidronate, ibandronate, zyronronone, iradronate, ipodronate, zonedronone, for example, risedronate, pamidronate, ibandronate, zonedronone, for example. etidronic acid, alendronic acid, tiludronic acid), fluorides such as disodium fluorophosphate, sodium fluoride; calcitonin, dihydrotachystirol; growth factors and cytokines, such as epidermal growth factor (ECE), growth factor derived from platelets (ROSE), fibroblast growth factors (ESRP), transforming growth factor β (TSRz-β), transforming growth factor a (TCE-α) , erythropoietin (EPO), insulin-like growth factor-Ι (1CE-1), insulin-like growth factor-ΙΙ (1CE-11), interleukin-1 (1L-1), interleukin-2 (1B-2), interleukin-6 ( 1b-6), interleukin-8 (ΙΕ-8), tumor necrosis factor α (Т№-а), tumor necrosis factor β (Т№-в), interferon-γ (ΙΝΕ-γ), colony-stimulating factors (С8Рз) ; monocytic chemotactic protein, fibroblast stimulating factor 1, histamine, fibrin or fibrinogen, endothelin-1, angiotensin-ΙΙ, collagens, bromocriptine, methylsergide, methotrexate, carbon tetrachloride, thioacetamide, ethanol, and also silver (ianthans and anti-infective agents, such as, in particular, β-lactam antibiotics, for example, β-lactamase-sensitive penicillins, such as benzylpenicillins (penicillin C), phenoxymethylpenicillin (penicillin V); β-lactamase-resistant penicillins, such as aminopenicillins, such as amoxicillin, ampicillin, bacampicillin; acylaminopenicillins, such as mezlocillin, piperacillin; karboksipenitsilliny, cephalosporins such as cefazolin, cefuroxime, cefoxitin, cefotiam, cefaclor, cefadroxil, cefalexin, loracarbef, cefixime, cefuroxime axetil, ceftibuten, tsefpodoksimproksetil, tsefpodoksimproksetil; aztreonam, ertapenem, meropenem; β-lactomase inhibitors, such as sulbactam, sultamicillin tosylate, tetracyclines, such as doxycycline, minocycline, tetracycline, chlortetracycline, oxytetracycline; neomycin, streptomycin, tobramycin, amikacin, netilmicin, paromomycin, framycetin, spectinomycin; macrolide antibiotics, such as azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin, yosamycin; lincosamides, such as clindamycin, lincomycin; gyrase inhibitors such as fluoroquinolones, for example, ciprofloxacin, ofloxacin, moxifloxacin, norfloxacin, gatifloxacin, enoxacin, fleroxacin, levofloxacin; quinolones, such as pimemidinic acid; sulfonamides, trimethoprim, sulfadiazine, sulfalene; glycopeptide antibiotics such as vancomycin, teicoplanin; polypeptide antibiotics, such as polymyxins, for example, colistin, polymyxin-b, nitroimidazole derivatives, for example, metronidazole, tinidazole; aminoquinolones, such as chloroquin, mefloquin, hydroxychloroquin; biduanide compounds such as proguanil; quinine alkaloids and diaminopyrimidines, such as pyrimethamine; amphenicols, such as chloramphenicol; rifabutin, dapsone, fusidic acid, fosfomycin, nifuratel, telithromycin, fusafungin, fosfomycin, pentamidine diisethionate, rifampicin, taurolidine, atovaquone, linezolid; virusostatics such as acyclovir, ganciclovir, famciclovir, foscarnet, inosine (dimepranol-4 acetamido benzoate), valganciclovir, valacyclovir, cidofovir, brivudine; antiretroviral active ingredients (inhibitors and derivatives of nucleoside analogue reverse transcriptase inhibitors), such as lamivudine, zalcitabine, didanosine, zidovudine, tenofovir; stavudine, abacvari; non-nucleoside reverse transcriptase inhibitor analogs: amprenavir, indinavir, saquinavir, lopinavir, ritonavir, nelfinavir; oseltamivir or lamivudine, as well as any combination and mixture of these agents.

According to preferred embodiments of the present invention, the active ingredient can be used in the form of a solution, dispersion or suspension in a suitable solvent or mixture of solvents, possibly followed by drying. Suitable solvents are indicated above.

Medical devices made in accordance with this invention can be functionalized for therapeutic and / or diagnostic purposes, as described in published applicants' applications UO 2004/105826 and I8 2005/0079201, the contents of which are included as references in this application. The functionalization of stents, orthopedic implants and the variants described in these sources can also be applied to medical devices according to this invention.

According to some embodiments of the present invention, the medical device can also be applied in living organisms or in combination with living organisms w νίνο and w νίΐτο. For this purpose, the device is usually in contact or cultured with νίίτο with living organisms, preferably cells, viral vectors or microorganisms, and then cultured in appropriate

- 26 012091 conditions for accelerating the growth of a living organism and / or growing into the porous structure of a composite material. According to one embodiment of the invention, the medical device can be used as a substrate for growing animal or plant cells and / or tissue, such as cells of organs or tissues selected from human or animal skin, liver tissue, bone tissue, blood vessels, etc. or microorganisms, enzymes, etc. ίη νίνο or ίη νίίτο. It is preferable to obtain a device such that it can be used as a cell frame for growing tissues, especially in a living organism or in a bioreactor for therapeutic or diagnostic purposes, or any combination thereof. The medical devices described in this application can thus be used as three-dimensional tissue structures (cell scaffolds) for directing the organization, growth and differentiation of cells, for example, during the formation of functional tissue. The functional tissue thus obtained may serve as a substitute for the desired tissue, for example, to replace poorly functioning organs and tissues, for example, skin, liver, bones, blood vessels, etc., or parts thereof.

The average pore size of composite materials can be determined by 8EM (scanning electron microscopy), adsorption methods such as gas adsorption or mercury porometry, chromatographic porometry. Porosity and specific surface can be determined by the absorption method Ν ₂ or He, for example, by the BET method. Particle sizes, for example, agents that form a network structure, can be determined, for example, on a C18 RateAppet analyzer (Aptegkttf or TOT method (transition time), X-ray diffraction, laser diffraction, TEM (Transmission Electron Microscopy). Particle size in suspensions, emulsions or dispersions can be determined by dynamic light scattering. The solids content in liquid mixtures can be determined by gravimetric methods or by measuring humidity.

Hereinafter the invention will be described in the examples, not limiting the invention.

Example 1

We prepared a homogeneous dispersion of soot Lat-Bleac (Oedicca, Settapu) with a particle size of from 90 to 120 nm and phenoxy resin (Vescoroh® EP, 401, Sules). First, a parent solution of methyl ethyl ketone (31 g), 3.1 g of Vescoroh® EP 401 and 0.4 g of glycerin (crosslinking agent, 81 dta A1bps11) was obtained. Soot paste was prepared from 1.65 g of Lat Bacc and 1.65 g of dispersant (Okrebuk® 2150, solution of block copolymer in 2-methoxy-1-methyl ethyl acetate, Vuk-Siette, Segtapu) by adding parts of the parent solution of methyl ethyl ketone / Vescoroh® EP 401 Then the paste was made into a dispersion by adding the rest of the parent solution using Repltai11k® solvent for 15 minutes to obtain a homogeneous dispersion. The solids content in the dispersion was about 3.5% when measured on a moisture measuring device (8 degrees MA 50). The particle size distribution in the dispersion was =50 = 150 nm, which was determined using a Hopa bB 550 laser diffractometer.

The dispersion was sprayed onto a steel substrate with an average density of 4 g / m ² . Immediately after spraying, the layer was dried for 2 minutes with hot air. Then, the sample was thermally treated in a nitrogen atmosphere in a usually tubular furnace with heating and cooling with a linear change of 1.33 k / min to a maximum temperature Tmax equal to 280 ° C, at which the sample was held for 30 minutes. The sample was examined by electron scanning microscopy (8EM). FIG. Figure 1 shows a layer image of the resulting porous mesh composite material with a magnification of 50000x; the average pore size was 100-200 nm.

Example 2

A homogeneous dispersion was obtained from the components in the same amounts as in Example 1. However, instead of carbon black, 1.6 g of silica was used (AegocP K 972, Oedicca, Segtapu). The dispersion contained solids in an amount of about 3.2%; the particle size distribution of Ό50 was 150 nm. The dispersion was sprayed onto a steel substrate with a density of 3.3 g / m ² and dried with hot air for 2 minutes. Heat treatment was performed as described in Example 1. A photograph obtained by scanning electron microscopy shows the resulting porous composite layer with an average pore size of 150 nm with an increase of 20,000x.

Example 3

Homogeneous dispersion of carbon black, Latr-Balac (Oedicca, Segtapu) with an initial particle size of from 90 to 120 nm, fullerenes (No. Pot M1x, ECC) and phenoxy-resin (Vescoroh® ЕR401, Sules) were prepared as described in Example 1. Initially, parental a solution of methyl ethyl ketone (31 g), 3.1 g of Vescoroh® ЕР401 (solids content of about 50%), and 0.4 g of glycerin (81dta A1bps11) as a crosslinking agent. The paste containing the particles of the network-forming agent was prepared from 0.9 g of lamp black, 0.75 g of a mixture of fullerenes and 1.65 g of dispersant (Okretchuk 2150, Vuk-Skette, Segtapu) with the addition of methyl ethyl ketone / Vescoroh portions ® ER401. Then the paste was made into a dispersion by adding the remaining parent solution using Rep1tai11k® solvent for 15 minutes to obtain a homogeneous dispersion. The amount of solids in the dispersion was about 3.6 wt.%), Which was determined on the installation for measuring humidity (850 MA 50). The particle size distribution in the Ό50 dispersion was 1 μm, which was determined

- 27 012091 using a Hopa B550 laser diffractometer.

The dispersion was sprayed with a density of about 3.5 µg / mm ² onto 10 commercially available coronary stents (ΚΑΌΝ, 18.5 mm, Eoy1teb1x Co., No. Neg1apbk) using Meb1Coa1® δΐeηΐ-Coaée ^ ^ Opo-Tek, υδΑ) and then dried with hot air using a fan (AAE 101, Ae11e Co., Segtapu) for 2 min. Then, the coated stents were thermally treated in a nitrogen atmosphere in a conventional convection tube furnace (Shp Co, Segtapu) while heating and cooling with a linear temperature change of 1.33 k / min to the maximum temperature Ttah equal to 280 ° C, at which the stents were held in for 30 minutes The coating was then cured for another 2 hours at 80 ° C in a convection oven; thereafter, the stents were examined by scanning electron microscopy. FIG. Figures 3a, b, and c show photographs of a porous, sponge-like composite coating layer obtained by the δEM method with magnification of 150x, 1000x, and 5000x.

Example 4

One of the coated stents obtained in Example 3 was treated for 30 minutes in an ultrasonic bath in acetone at 35 ° C immediately after heat treatment, then dried and cured for 2 more hours at 80 ° C in a convection oven . FIG. 4a, b and c are photographs of the porous spongy layer of the composite coating with magnification of 150x, 1000x and 20,000x.

Example 5

Obtaining a sponge-like, porous-like sponge coating for joint implants with a spongy inner surface of the tissue skeleton adjacent to the bone tissue.

Homogeneous dispersion of carbon black, Latr-Balac (Oedicca, Segtapu) with an initial particle size of 90 to 120 nm and fullerenes (No. shot M1x, GSS) and phenoxy resin (Vescoroh® ЕR401, Su! Es) were obtained as in Example 3, using the same components in the same quantities. 20 cylindrical stainless steel 316b samples were immersed in the dispersion and then dried with hot air using a fan (AAE 101, Aell Co., Segtapu) for 2 minutes. Then the coated samples were subjected to heat treatment under nitrogen in a conventional convection tube furnace (Copp., Segtapu) with a linear change in heating and cooling at 1.33 k / min to a maximum temperature Tmax equal to 280 ° C, which was maintained for 30 min. Then, the samples were treated for 30 minutes in an ultrasonic bath in acetone at a temperature of 35 ° C immediately after heat treatment for 30 minutes and then dried and cured for another 2 hours at a temperature of 80 ° C in a convection oven. Then the samples were sterilized in ethanol (98%) and separately incubated with 1 ml of osteoblastic cell culture with an average cell number of about 10 ⁶ for 7 days. Previously, the cell culture was suspended in 1 ml of Ca-set AM and kept for 30 min in CO ₂ medium in order to detect the vital color using fluorescence microscopy. After 120 minutes, 3 days, 5 days and 7 days, the samples were examined under a microscope. Already after 120 min, adhesion of osteoblastic cells on the surface of the coated samples was observed, which increased after 3, 5 and 7 days with a turbulent or trabecular orientation, respectively. FIG. 5a, b and c are photographs showing the growth of cell culture on the samples after 120 minutes, 3 days and 5 days, respectively.

Example 6

To obtain a porous mesh sponge composite for use as a bone substitute, 30 g of epoxy novolac resin (Е.. E.N. 438, Eo \ y C11-et1ca1) was heated at 80 ° C with stirring. 1 g of tantalum powder (HC δΙοΗ, Segtapu) with an average particle size of about 3 μm, 1 g of T1O ₂ powder (Aehoh1be P25, Eedikka AS, Segtapu) with an average particle size of about 25 nm was added, dispersed with stirring at 80 ° C and 2 ml of a solution of a crosslinking agent containing 10% by weight of phenylenediamine (Asgok Ogdashsk), 40% by weight of diethylamine (Asgok Ogdap1sk), 1% by weight of dicyandiamide (Asgok Ogdashsk), 9% by weight of ethyleneamine (Asgok Ogdashsk) and 40 wt.% Вескоох® EX651 (Su! eu). Then the mixture was poured into a mold and cured in a convection oven at 80 ° C for 24 hours. Then the molded product was thermally treated in air at 200 ° C. The sample was cut into two parts and the cut plane was examined using the δEM method. FIG. 6 with a magnification of 100x shows a photograph of this surface. The average pore size was about 5 microns.

Example 7

1.87 g of phenoxy resin (Veskorokh EP 401, Su! Ex) were placed in a mortar and 0.635 g of tantalum particles with an average particle size of about 3 microns (N.S. δΙοΕ) were added in parts, the mixture was ground to obtain an almost homogeneous paste.

Separately, 0.626 g of titanium oxide particles with an average size of about 21 nm (Aehoh1be P25, Oedikka, Segtapu) were combined with 1.268 g of dispersing agent (Eukregbyuk P-104, Vuk Cetrieu, Segtapu), crushed to form a paste and diluted with 4.567 g of methyl ethyl ketone in order to obtain dispersion. The dispersion was combined with a homogeneous paste of tantalum particles in phenoxy resin, and 0.649 g of ethoxypropyl acetate, 0.782 g of glycerin (a crosslinker), and also 0577 g of polyethylene particles (Mkgoksgy, an average particle size of about 150 microns, and Compradium weight) and 0.126 g of polyethylene oxide (mol. Weight 300000 , δίβΐηη A1bps11). The resulting mixture was subjected to homogenization in a rocking mill (CXY) at a frequency of 25 kHz in those

- 28012091 2 minutes in the presence of 3 steel balls having a diameter of 1 cm. The resulting dispersion was pipetted onto a round titanium billet and dried for 30 minutes in a convection oven at a temperature of about 50 ° C. The sample was then processed at a temperature of about 300 ° C under nitrogen to completely cure the resin. The resulting material had microscopic pores about 100,200 microns in size, as shown in FIG. 7a and b. Scanning electron microscopy revealed the presence of smaller pores of the mesh spongy material in combination with microscopic pores, which ensured hierarchical porosity, as can be seen in FIG. 7a (magnification 100x) and in FIG. 7b (magnification 20000x).

Example 8

As described above in Example 7, a paste containing tantalum was obtained, however, using Euvrgbyuk® 180 (Wook Sispis. Ssgtapu) as a dispersant and was combined with a dispersion containing titanium dioxide, as described in Example 7. Then, as fillers and pore formers were added 0.649 g of ethoxypropyl acetate, 0.782 g of glycerol (crosslinker) and 0.057 g of polyethylene particles (M1cgrc, average particle size about 150 µm, 1 ct Compote) and 0.126 g of polyethylene oxide (mol. weight 300000, 81 gram L16ps11). The resulting mixture was homogenized in a rocking mill (Yas1bc11) at a frequency of 25 kHz for 2 minutes in the presence of 3 steel balls having a diameter of 1 cm. ° s The samples had a microscopically porous surface with an average pore size of about 100 microns, as shown in FIG. 8a. FIG. 8b shows this material at a magnification of 100 times and it can be seen that there are simultaneously macroscopic pores in the mesh material with a microporous structure.

Having examined in detail some variations of this invention, it should be noted that the invention described above is not limited to the specific details described in this specification, since many obvious changes can be made without departing from the scope of the invention. Variants of the present invention are described in this description or are obvious from it and are covered in a detailed description and figures. The detailed description given as an example does not limit the invention to only the described variants.

The above patent documents and documents cited in or during their consideration (documents cited in sources) and all documents cited or mentioned in documents cited in sources and all documents, references and publications referred to in them (cited documents), and all documents cited in the latter, along with any manufacturer's instructions, descriptions, specifications and leaflets for the products mentioned in this application or in any reference, are included in this application as references and may be employed in the practice of the invention. Citing or indicating any document in this application is not an assumption that such a document is a prototype of the present invention. It should be noted that the terms used in this description and especially in the claims, such as containing, containing, containing and the like, have the broadest possible meaning, for example, they can mean includes, included, including, etc. ; and that terms such as consisting essentially of and consisting essentially of may have the broadest possible meaning, for example, to allow for the presence of elements not explicitly mentioned, but to exclude those elements that are found in the prior art or affect the basic or new characteristic of the invention .

Claims (45)

CLAIM 1. A medical device comprising a porous composite material that contains at least one agent that forms a network structure and at least one matrix-forming material that contains at least one synthetic organic polymer. 2. The device according to claim 1, characterized in that the composite material obtained by a method comprising the steps of: a) obtaining a liquid mixture containing ί) at least one agent forming a network structure; and ίί) at least one matrix material containing at least one organic polymer, and b) curing the specified mixture. 3. The device according to claim 1 or 2, characterized in that it consists almost entirely of a composite material. 4. Device according to any one of claims 1 to 3, characterized in that it comprises a coating obtained from a composite material. 5. A medical device comprising a coating that includes a porous composite material that contains at least one agent that forms a network structure and at least one matrix-forming material that contains at least one organic polymer. 6. Device according to any one of claims 1 to 5, characterized in that the agent forming the network structure, - 29 012091 embedded in the matrix material. 7. Device according to any one of claims 1 to 6, characterized in that the porous composite material has a mesh structure. 8. The device according to claim 4 or 5, characterized in that the coating is on at least part of the surface of the device. 9. Device according to any one of claims 1 to 8, characterized in that the agent forming the network structure is in the form of particles. 10. The device according to claim 9, characterized in that the particles include nano - or microcrystalline particles. 11. Device according to any one of claims 1 to 10, characterized in that the agent forming the network structure contains at least two fractions of particles of the same or different materials, while the fractions differ in particle size by a coefficient equal to at least 1.1. 12. The device according to claim 11, characterized in that the fractions differ in particle size by a factor equal to at least 2. 13. Device according to any one of claims 1 to 8, characterized in that the agent forming the network structure is selected from tubes, fibers or wire. 14. The device according to any one of claims 1 to 13, characterized in that the agent forming the network structure includes at least one ingredient from metal, metal compound, metal alloy, metal oxide, silicon dioxide, zeolite, titanium oxide, zirconium oxide , aluminum oxide or aluminum silicate, metal carbide, metal nitride, metal oxynitride, metal carbonitride, metal oxycarbide, metal oxynitride, metal oxycarbonitride, organic metal salt, inorganic metal salt, compound of a semiconducting metal, such as MD8 , Md8e, MdTe, Sa8, Sa8e, CdTe, 8g8, 8g8e, 8gTe, Va8, Va8e, wool, Ζηδ, Ζη8e, ΖηTe, C68, Sb8e, SbTe, N§8, Nd8e, HgTe, Saakov, SaY, GaP, 6a8 , 1пСа Ак, ΙηΡ, ΙηΝ, 1п8Ь, 1пАк, А1Ак, А1Р, А18Ь, А18, germanium, lead or silicon; nanoparticles with a shell based on metals, glass, glass fibers, carbon, carbon fibers, graphite, carbon black, lamp black, fullerenes such as C36, C60, C70, C76, C80, C86, C112, nanotubes selected from M \ UYT. 8 \ LOW AHUYT. randomly oriented nanotubes; layered fullerenes, metallofullecrenes, metal-containing endohedral fullerenes or endometallofullerenes, talc, minerals, organometallic compounds or metal alkoxide. 15. The device according to p. 14, characterized in that the agent forming the network structure includes at least one ingredient of particles of a magnetic, supermagnetic or ferromagnetic metal or alloy, including at least one metal of iron, cobalt, nickel, manganese, mixtures of platinum-iron, iron-platinum alloys, metal oxides, such as iron oxide, gamma-iron oxide, magnetites or ferrites of iron, cobalt, nickel or manganese. 16. Device according to any one of claims 1 to 15, characterized in that the composite material further includes at least one agent forming a network structure selected from particles of organic materials or fibers made from organic materials. 17. The device according to p. 16, wherein the organic materials include at least one of the polymers, oligomers or prepolymers, shellac, cotton or fabrics. 18. The device according to claim 17, wherein the polymers include at least one of a synthetic homopolymer or copolymer of an aliphatic or aromatic polyolefin, such as polyethylene or polypropylene; or biopolymer. 19. A device according to any one of claims 1-18, wherein the agent forming the network structure comprises a combination of at least one particulate material with at least one material having a shape selected from tubes, fibers or wire. 20. A device according to any one of claims 1 to 19, wherein the matrix material includes at least one of oligomers, polymers, copolymers or prepolymers, thermosetting polymers, thermoplastic polymers, synthetic rubbers, extrudable polymers, injection molded polymers, or molded polymers. 21. Device according to any one of claims 1 to 20, characterized in that the matrix material includes at least one polymer of poly (meth) acrylate, unsaturated polyester, saturated polyester, polyolefins, polyethylene, polypropylene, polybutylene, alkyd resins, epoxy polymers, epoxy resins, phenoxy resin, rubber latex, polyamide, polyimide, polyether imide based on polyether, polyamidoimide, polyether imide based on polyester, polyether imidoimide, polyurethane, polycarbonate, polystyrene, polyphenol, polyvinyl ether polysilicone, polyacetate, 22. Device according to any one of claims 1 to 21, characterized in that it is selected from implants suitable for introduction into the human or animal body. 23. Device according to any one of paragraphs.1-21, characterized in that it includes medical devices - 30 012091 va or implants for therapeutic and / or diagnostic purposes selected from at least one of vascular endoprostheses, stents, coronary stents, peripheral stents, surgical implants, orthopedic prostheses of bones, prosthetic joints, bone substitutes, substitutes for vertebrae in the thoracic and dorsal regions of the spinal column, artificial hearts, artificial heart valves, subcutaneous implants, intramuscular implants, implantable delivery devices and drugs, catheters, driver guides for catheters or parts thereof, surgical instruments, surgical needles, screws, nails, clips, brackets, substrates for growing living material or cell frames for growing tissues. 24. Device according to any one of claims 1 to 23, characterized in that the composite material further comprises at least one active agent selected from at least one of the biologically active agents, therapeutically active agents or agents intended for diagnostic purposes. 25. The device according to claim 24, characterized in that it is capable of releasing the active agent in a controlled manner. 26. The device according to claim 24, wherein the agent intended for diagnostic purposes includes at least one ingredient from markers, a contrast medium or a radiopaque material. 27. Device according to any one of claims 1 to 26, characterized in that at least one of the agents forming the network structure or the matrix material is a marker, a contrast medium or a radiopaque material. 28. The device according to p. 26 or 27, characterized in that the marker, contrast medium or radiopaque material is detected or form a signal that is detected by physical, chemical or biological detection methods. 29. The device according to p. 28, characterized in that the signal can be detected by at least one method from the X-ray method, the method of nuclear magnetic resonance (NMR), the method of computed tomography, scintigraphy, single-proton emission computed tomography (8EST), ultrasound , radio frequency method (CR) or optical coherence tomography (OST). 30. The device according to p. 26 or 27, characterized in that the marker additionally has at least one biological or therapeutic effect on the human or animal body. 31. Device according to any one of claims 1 to 30, characterized in that it is selected from a stent, a drug-releasing stent, an implant for drug delivery or an orthopedic drug-releasing implant. 32. The device according to any one of claims 1 to 31, characterized in that it further includes at least one anionic, cationic or amphoteric coating obtained from at least one polymer of alginate, carrageenan, carboxymethylcellulose, poly (meth) acrylates, chitosan, poly-L-lysine or phosphorylcholine. 33. Device according to any one of claims 1 to 32, characterized in that it comprises at least one living material from a microorganism, a viral vector, cells or living tissue. 34. Device according to any one of paragraphs.1-33, characterized in that at least one agent forming the network structure is a material capable of forming a structure resembling a grid. 35. Device according to any one of paragraphs.1-34, characterized in that at least one agent that forms a network structure, is a material capable of self-orientation with the formation of a three-dimensional structure. 36. Device according to any one of claims 1 to 35, characterized in that the ratio between the total volume of the agent (s) forming the mesh structure and the matrix material (s) in the composite material is in the range from 20:80 to 80 :20. 37. Device according to any one of claims 1 to 36, characterized in that the composite material includes an agent that forms a network structure selected from carbon black, fullerenes, carbon fibers, silicon dioxide, titanium dioxide, metal particles, tantalum particles or polyethylene particles, and The matrix material is selected from at least one epoxy resin resin or phenoxy resin. 38. The device according to claim 37, wherein the composite material is obtained from a liquid mixture containing at least one organic solvent, which was cured by removing the solvent during heat treatment without decomposing the matrix material. 39. Device according to any one of claims 1 to 38, characterized in that the porous composite material contains at least one therapeutically active agent that can be dissolved or extracted from the composite material in the presence of physiological fluids. 40. Device according to any one of paragraphs.1-39, characterized in that it has pores with a size equal to at least 1 nm. 41. Device according to any one of paragraphs.1-39, characterized in that it has pores with a size equal to - 31 012091 from about 1 nm to 400 microns. 42. Device according to any one of paragraphs.1-39, characterized in that it has a degree of porosity equal to from about 30 to about 80%. 43. The use of a medical device according to any one of the preceding claims as a substrate for culturing ίη νίνο and / or η ν клеток cells. 44. The use according to claim 43, characterized in that the device is used as a cellular framework for creating tissue. 45. The use according to claim 44, wherein the cell frame is used in a living organism or in a bioreactor.